History ThatOneBoss / TheBindingOfIsaac

* Pestilence is mostly a pain because of room design more than anything else. The rocks and holes in the arena limit mobility, and his ipecac shots cover the floor with toxic green creep. Fortunately, his ipecac blasts will clear the rocks out eventually. Unfortunately, he is spawning grubs all over, and he has a sudden tendency to rapid fires his ipecac blasts. Once you get to his second stage, it is easy... but good luck getting to his second stage on more than a heart or two. He's even worse in ''Rebirth'', as his ipecac blasts are faster.

* The Visage. Whereas the Mask of Infamy is, as noted above, hard but has a singular pattern, its "[[BackFromTheDead undead(?)]]" counterpart [[CameBackStrong came back]] '''''[[CameBackStrong very]]''''' [[CameBackStrong strong]] and much more unpredictable. You first need to break the chain holding the heart and the mask, the latter of which can still attack you while chained to the heart. Once broken, however, prepare for pain. The heart and mask can perform various {{Combination Attack}}s with the other (including [[ThatOneAttack Brimstone beams]]), by using the chain's remnants to pull the mask in and potentially hit you if you're in the way. Additionally, the armored heart's chain hookshot attack has barely ''ANY'' windup and moves '''INCREDIBLY FAST'''. If this happens during a ''[[OneHitPointWonder Tainted Lost]]'' run, your run is compromised. Once you deplete enough health from the heart, it will ShedArmorGainSpeed, and start firing energy balls that hover towards the mask and empower it when they touch it, causing it to fire more lasers. If you fail to destroy the energy balls, the heart can also absorb them to [[HealThyself heal itself]] and fire rings of fire and more lasers. Fortunately, the mask itself can be deactivated quickly with enough damage (and bombs will do the trick in one go), and killing the heart kills the mask by default, but deactivating the mask will also cause the heart to [[ChainPain weaponize the chain on you]] for some of its attacks, and the energy balls the heart coughs up can also revive the mask if you fail to destroy them. Overall, a fun boss? [[AwesomeBosses/VideoGames Yes, usually.]] But a hard one? ''Absolutely.'' It doesn't help the floor you will encounter The Visage in is [[ThatOneLevel Gehenna]].

* The Visage. Whereas the Mask of Infamy is, as noted above, hard but has a singular pattern, its "[[BackFromTheDead undead(?)]]" counterpart [[CameBackStrong came back]] '''''[[CameBackStrong very]]''''' [[CameBackStrong strong]] and much more unpredictable. You first need to break the chain holding the heart and the mask, the latter of which can still attack you while chained to the heart. Once broken, however, prepare for pain. The heart and mask can perform various {{Combination Attack}}s with the other (including [[ThatOneAttack Brimstone beams]]), by using the chain's remnants to pull the mask in and potentially hit you if you're in the way. Once you deplete enough health from the heart, it will ShedArmorGainSpeed, and start firing energy balls that hover towards the mask and empower it when they touch it, causing it to fire more lasers. If you fail to destroy the energy balls, the heart can also absorb them to [[HealThyself heal itself]] and fire rings of fire and more lasers. Fortunately, the mask itself can be deactivated quickly with enough damage (and bombs will do the trick in one go), and killing the heart kills the mask by default, but deactivating the mask will also cause the heart to [[ChainPain weaponize the chain on you]] for some of its attacks, and the energy balls the heart coughs up can also revive the mask if you fail to destroy them. Overall, a fun boss? [[AwesomeBosses/VideoGames Yes, usually.]] But a hard one? ''Absolutely.'' It doesn't help the floor you will encounter The Visage in is [[ThatOneLevel Gehenna]].

* The Haunt. Initially, he's completely invincible and relies on his three [[DemonicSpiders smaller ghosts]] to assist him, but once they're killed, he starts his attacks. The Haunt is actually very fast once he starts attacking, making it difficult to lead your shots to him. Not only does he have an ''untelegraphed'' bullet spread attack, but he can also fire a Brimstone laser vertically across the screen with barely a second of warning. And if you think you can just run off to the side of the Haunt to dodge this, think again. Doing this causes him to charge you for a '''full heart''' of damage. And the worst part? He's a ''Cellar/Burning Basement'' boss, meaning he can potentially be the first boss encountered in a run. Some fans have come to the conclusion that he's even harder than the Widow, the previous infamous Cellar boss. And woe be to you if you encounter the pink champion version which fires slanted, ''bouncing'' Brimstone, forcing you to stay up close and potentially get hit by bullets. The Haunt may as well just be the new [[TheScrappy Bloat]]. What's worse is that while other bosses like the Bloat and the Matriarch were nerfed in some updates and [[DownloadableContent DLCs]], the Haunt was not nerfed in any way. As a matter of fact, not many of the ''Rebirth'' bosses, if ''any'', were nerfed at all, including some of the ones listed below.
* The Adversary, which is the posthumous version of the Dark One. The one and only thing that stands out about the Adversary is that it [[ThatOneAttack fires a Brimstone laser that]] ''[[AlwaysAccurateAttack homes in on you]]''. Unless you run behind the Adversary, this ''will'' hit you. This becomes incredibly problematic if there happens to be two of them in one room, as it gives you almost no room to dodge one Adversary's laser while avoiding the other Adversary's own attacks. If the Adversary manages to wander into one of the corners, get ready to take a hit, because there’s nowhere to hide!

* If you thought the TrueFinalBoss fight against Mega Satan in ''Rebirth'' was brutal, you're far from the worst. Enter '''[[EldritchAbomination Hush]]'''. Reach Mom's Heart or It Lives and beat them in under 30 minutes to get access to its lair, a place called ???. Before the fight, the room gives you two item rooms (with two item options to choose from on each room), four golden chests, and a shop. Needless to say, ''you will need them''. You'll first face Hush as a glorified ???, but defeating it is not the end of it, as it reveals [[OneWingedAngel its true form]]. With [[SequentialBoss five phases to the true form's battle]], loads and loads of BulletHell attacks that make bosses from ''Franchise/TouhouProject'' blush (and one of which [[ThatOneAttack wraps around the room's boundaries]]), the ability to [[FlunkyBoss spawn loads and loads of enemies]] to block your shots unless you have a piercing attack, the ability to merge with the floor to completely avoid your attacks, and the [[DamageSpongeBoss second-highest HP pool]] at [[NumberOfTheBeast 6666 HP]] on top of damage resistance that scales with your current damage, you're in for [[MarathonBoss the actual longest fight in the game]], no matter your item build. It's easy to get hit by its attacks as it is, so you also better hope you came in to its battle packing tons of health... unless you're playing as [[OneHitPointWonder The Lost]] or [[TierInducedScrappy The Keeper]], in which case... [[ThisIsGonnaSuck good luck]], '''[[NintendoHard you'll need it]]'''. Granted, you can skip this boss fight in ''Repentance'' by using IV - The Emperor?, you fight [[WarmUpBoss Monstro]] instead of Hush, and beating [[BreatherBoss him]] will count as beating Hush.

* Thought that bosses like The Bloat, The Adversary, The Cage, or Sisters Vis were painful? The Forgotten update adds The Matriarch, an unholy mix between Fistula, Chub, and the Chubber and Fistuloid enemies that's [[DamageSpongeBoss even sturdier]][[note]]at 700 HP[[/note]], and who can appear on ''any'' environment of the Womb (but as of ''Repentance'', appears most commonly in the Scarred Womb). The Matriarch shoots Chargers in the eight cardinal directions, spawns Fistuloids that surround her, and shoots a jumbo tear that leaves a puddle of toxic blood creep. As she takes damage, she sheds small Fistulas and Fistuloids which shoot Chargers like Chubber does. At medium health, she starts summoning [[ZergRush an enormous wave of Fistuloids that immediatly shoot their Chargers at you]]. When "killed", the Chub sheds her Fistula armor completely, spawning even more Chargers, Fistulas and Fistuloids. Lastly, unlike the normal version of Chub, this one [[DefiedTrope defies]] the FeedItABomb strategy by [[HoistByTheirOwnPetard spitting it back at you]]; only The Forgotten can avoid this attack by [[TennisBoss swinging the bomb back at her]] with his bone. It's virtually impossible to avoid getting hit simply because the Matriarch is big enough, her spawns are numerous enough, and her attacks are quick enough, that there is just nowhere in the room you can hide. Therefore, to many, this boss became the new Bloat for the final days of ''Afterbirth†'', being considered ''even'' harder than the non-tankiest final bosses in the game, and unlike bosses like Sisters Vis and Big Horn, was never nerfed - it took until ''Repentance'' where this hellspawn was '''''finally''''' {{nerf}}ed, causing her to [[CastFromHitPoints take 30 HP of damage when she summons a Fistuloid]], making the Fistuloids that orbit her attack less aggressively, and shedding less pieces of Fistula armor whenever her health is reduced a certain amount - nevertheless, she's remains a potentially very dangerous boss.
* '''Delirium'''. In addition to having [[DamageSpongeBoss an absolutely titanic amount of HP (10,000, the highest HP of any enemy tied with The Beast)]], his attacks are hard to dodge as they are; they have very convoluted and tight patterns of bullets fired with barely any downtime, some of which can be ipecac shots. No matter what Delirium transforms into, though, expect to be annoyed by his propensity to teleport around the room at random (often [[TeleFrag right besides you]]) and the fact [[TurnsRed he gets faster as his health gets lower]]. Even so, the amount and type of bosses that you encounter, combined with the [[GameBreaker build you amassed before the fight]], are what will make Delirium either a boss whose forms are [[CurbStompBattle only a nuisance while dealing with its bullet patterns]], or a [[NintendoHard true nightmare of a boss]] that [[MarathonBoss you'll have to outlast]]. It doesn't help that the level you find Delirium in, [[MarathonLevel The Void]], has [[GoddamnedBats enemies]] of [[DemonicSpiders all types]] that will cause you to hope you can hold onto your life, and bosses that Delirium can transform into during the fight... yes, that includes all and each of the other bosses on this page (up to ''Afterbirth†'')[[note]]sans Hush, unless you encounter ''very'' few bosses throughout your run[[/note]]. It gets to the point where most consider it even harder than '''The Beast''', ''Repentance'''s TrueFinalBoss.

* Baby Plum is very BulletHell-ish for a Basement boss, and has a decent amount of HP too. Her attack where she spits out projectiles while bouncing around the walls can be hard to dodge due to the disorganised nature of the projectiles, some of which even do a whole heart of damage. She also takes increased knockback during this attack, making her ricocheting even more unpredictable.

* [[DemBones The Pile]], who is curiously the "[[BackFromTheDead undead]]" version of Stain (meaning its an even "[[BuffySpeak undeader]]" version of Polycephalus), but who [[CameBackStrong manages to be even more dangerous and aggressive than Polycephalus or Stain]]. It can summon lines of spikes to sting you, burrow underground at high speeds to quickly emerge and pelt you with bone shots three times, and charge at you at pretty much the same speed that Dangle and Gurdy Jr. would, but making bones rain behind itself similarly to Bumbino. It can also summon [[GoddamnedBats Bonies]], which will prove to be just the right distraction in the battle. On top of all this? The Pile has a pretty respectable HP pool[[note]]580 HP[[/note]], not huge but just high enough to make it just as dangerous as bosses like The Cage in combination with its attacks. It mainly appears in chapter 3's Necropolis, but it can also appear in the Ashpit in the alternate path.

* The Visage. Whereas the Mask of Infamy is, as noted above, hard but has a singular pattern, its "[[BackFromTheDead undead(?)]]" counterpart [[CameBackStrong came back]] '''''[[CameBackStrong very]]''''' [[CameBackStrong strong]] and much more unpredictable. You first need to break the chain holding the heart and the mask, the latter of which can still attack you while chained to the heart. Once broken, however, prepare for pain. The heart and mask can perform various {{Combination Attack}}s with the other (including [[ThatOneAttack Brimstone beams]]), by using the chain's remnants to pull the mask in and potentially hit you if you're in the way. Once you deplete enough health from the heart, it will ShedArmorGainSpeed, and start firing energy balls that hover towards the mask and empower it when they touch it, causing it to fire more lasers. If you fail to destroy the energy balls, the heart can also absorb them to [[HealThyself heal itself]] and fire rings of fire and more lasers. Fortunately, the mask itself can be deactivated quickly with enough damage (and bombs will do the trick in one go), and killing the heart kills the mask by default, but deactivating the mask will also cause the heart to [[ChainPain weaponize the chain on you]] for some of its attacks, and the energy balls the heart coughes up can also revive the mask if you fail to destroy them. Overall, a fun boss? [[AwesomeBosses/VideoGames Yes, usually.]] But a hard one? ''Absolutely.'' It doesn't help the floor you will encounter The Visage in is [[ThatOneLevel Gehenna]].
* The alternate path's Mom is much more deadly than her Depths counterpart. Her monster summons include Psychic Horfs, [[DemonicSpiders Raglings]] and Cursed Globins which are much more deadly than the Depths could ever be. If you face her in the alternate floor, [[ThatOneLevel Gehenna]], you'll also have to contend with that floor's DemonicSpiders too. Her "safe" eye will now fire twin Brimstone lasers if you are in sight. And finally, her stomp has a chance to instead be three quick stomps, with the third one [[ThatOneAttack leaving rows of explosions in four directions that can't be blocked by Host Hat or Pyromaniac]], because why not? The good thing is that she will never use her hand attack, and that she can't stomp the ground thrice if she's firing her Brimstone, and viceversa. However, if there was a time to use the Bible, then now would be the time.

'''Note:''' {{Final Boss}}es and [[WakeUpCallBoss Wake-Up Call Bosses]] aren't allowed unless they are overly hard by their standards. Also, all {{spoiler}}s are [[Administrivia/SpoilersOff unmarked]]! '''Administrivia/YouHaveBeenWarned!'''

* Bumbino's attacks are aplenty and fairly unpredictable, not helped by the arena you will be pitted in. The room will always be full of rocks, which will do nothing to protect you, as he will always break them out of his way. His dash attack covers an excellent range and is also very fast, and makes rocks rain all over the battlefield, so even if he leaves himself open afterwards, you will not have much time to get some counterhits. His swipe attacks also [[BanditMook cause you to lose coins, which he will take for himself]] and will not be replenished when he's defeated - he prioritizes getting the coins before attacking you, too. He can also throw a bomb at you, much like he can do so when he's a familiar. Finally, all of his attacks deal one full heart of damage, so if you're not careful, you're going to lose lots of health to this boss. Additionally, this is only in chapter 2, and he can appear in all of its environments.
** If you're somehow able to survive the onslaught after losing 12 cents worth of coins, Bumbino will happily drop an item in addition to the Boss item and leave you alone, easing the burn a little. However, if you somehow manage to spawn a Sticky Nickel, he will comically try to pick it up to no avail, essentially [[AntiClimaxBoss rendering the fight unloseable]].

* The alternate path's Mom is much more deadly than her Depths counterpart. Her monster summons include Psychic Horfs, [[DemonicSpiders Raglings]] and Cursed Globins which are much more deadly than the Depths could ever be. If you face her in the alternate floor, [[ThatOneLevel Gehenna]], you'll also have to contend with that floor's DemonicSpiders too. Her "safe" eye will now fire twin Brimstone lasers if you are in sight. And finally, her stomp has a chance to instead be three quick stomps, with the third one [[ThatOneAttack leaving rows of explosions in four directions that can't be blocked by Host Hat or Pyromaniac]], because why not? The good thing is that she will never use her had attack, and that she can't stomp the ground thrice if she's firing her Brimstone, and viceversa. However, if there was a time to use the Bible, then now would be the time.

* The alternate path's Mom is much more deadly than her Depths counterpart. Her monster summons include Psychic Horfs, [[DemonicSpiders Raglings]] and Cursed Globins which are much more deadly than the Depths could ever be. If you face her in the alternate floor, [[ThatOneLevel Gehenna]], you'll also have to contend with that floor's DemonicSpiders too. Her "safe" eye will now a fire twin Brimstone laser you are in sight. And finally, her stomp has a chance to instead be three quick stomps, with the third one [[ThatOneAttack leaving rows of explosions in four directions that can't be blocked by Host Hat or Pyromaniac]], because why not? The good thing is that she will never use her had attack, and that she can't stomp the ground thrice if she's firing her Brimstone, and viceversa. However, if there was a time to use the Bible, then now would be the time.

* The Haunt. Initially, he's completely invincible and relies on his three [[DemonicSpiders smaller ghosts]] to assist him, but once they're killed, he starts his attacks. The Haunt is actually very fast once he starts attacking, making it difficult to lead your shots to him. Not only does he have an ''untelegraphed'' bullet spread attack, but he can also fire a Brimstone laser vertically across the screen with barely a second of warning. And if you think you can just run off to the side of the Haunt to dodge this, think again. Doing this causes him to charge you for a '''full heart''' of damage. And the worst part? He's a ''Cellar/Burning Basement'' boss, meaning he can potentially be the first boss encountered in a run. Some fans have come to the conclusion that he's even harder than the Widow, the previous infamous Cellar boss. And woe be to you if you encounter the pink champion version which fires slanted, ''bouncing'' Brimstone, forcing you to stay up close and potentially get hit by bullets. The Haunt may as well just be the new [[TheScrappy Bloat]]. What's worse is that while other bosses like the Bloat and the Matriarch were nerfed in future updates and [[DownloadableContent DLCs]], the Haunt was not nerfed in any way. As a matter of fact, not many of the ''Rebirth'' bosses, if ''any'', were nerfed at all, including some of the ones listed below.

* The Haunt. Initially, he's completely invincible and relies on his three [[DemonicSpiders smaller ghosts]] to assist him, but once they're killed, he starts his attacks. The Haunt is actually very fast once he starts attacking, making it difficult to lead your shots to him. Not only does he have an ''untelegraphed'' bullet spread attack, but he can also fire a Brimstone laser vertically across the screen with barely a second of warning. And if you think you can just run off to the side of the Haunt to dodge this, think again. Doing this causes him to charge you for a '''full heart''' of damage. And the worst part? He's a ''Cellar/Burning Basement'' boss, meaning he can potentially be the first boss encountered in a run. Some fans have come to the conclusion that he's even harder than the Widow, the previous infamous Cellar boss. And woe be to you if you encounter the champion version which fires slanted, ''bouncing'' Brimstone, forcing you to stay up close and potentially get hit by bullets. The Haunt may as well just be the new [[TheScrappy Bloat]]. What's worse is that while other bosses like the Bloat and the Matriarch were nerfed in future updates and [[DownloadableContent DLCs]], the Haunt was not nerfed in any way. As a matter of fact, not many of the ''Rebirth'' bosses, if ''any'', were nerfed at all, including some of the ones listed below.

* The Haunt. Initially, he's completely invincible and relies on his three [[DemonicSpiders smaller ghosts]] to assist him, but once they're killed, he starts his attacks. The Haunt is actually very fast once he starts attacking, making it difficult to lead your shots to him. Not only does he have an ''untelegraphed'' bullet spread attack, but he can also fire a Brimstone laser vertically across the screen with barely a second of warning. And if you think you can just run off to the side of the Haunt to dodge this, think again. Doing this causes him to charge you for a '''full heart''' of damage. And the worst part? He's a ''Cellar/Burning Basement'' boss, meaning he can potentially be the first boss encountered in a run. Some fans have come to the conclusion that he's even harder than the Widow, the previous infamous Cellar boss. And woe be to you if you encounter the champion version which fires slanted, ''bouncing'' Brimstone, forcing you to stay up close and potentially get hit by bullets. The Haunt may as well just be the new [[TheScrappy Bloat]]. What's worse is that while other bosses like the Bloat and the Matriarch were nerfed in future updates and [[DownloadableContent DLCs]], the Haunt was not nerfed in any way. As a matter of fact, not many of the ''Rebirth'' bosses, if ''any of them'', were nerfed at all, including some of the ones listed below.

* The Haunt. Initially, he's completely invincible and relies on his three [[DemonicSpiders smaller ghosts]] to assist him, but once they're killed, he starts his attacks. The Haunt is actually very fast once he starts attacking, making it difficult to lead your shots to him. Not only does he have an ''untelegraphed'' bullet spread attack, but he can also fire a Brimstone laser vertically across the screen with barely a second of warning. And if you think you can just run off to the side of the Haunt to dodge this, think again. Doing this causes him to charge you for a '''full heart''' of damage. And the worst part? He's a ''Cellar/Burning Basement'' boss, meaning he can potentially be the first boss encountered in a run. Some fans have come to the conclusion that he's even harder than the Widow, the previous infamous Cellar boss. And woe be to you if you encounter the champion version which fires slanted, ''bouncing'' Brimstone, forcing you to stay up close and potentially get hit by bullets. The Haunt may as well just be the new [[TheScrappy Bloat]]. What's worse is that while other bosses like the Bloat and the Matriarch were nerfed in future updates and DLCs, the Haunt was not nerfed in any way. As a matter of fact, not many of the ''Rebirth'' bosses, if ''any of them'', were nerfed at all, including some of the ones listed below.

* The Haunt. Initially, he's completely invincible and relies on his three [[DemonicSpiders smaller ghosts]] to assist him, but once they're killed, he starts his attacks. The Haunt is actually very fast once he starts attacking, making it difficult to lead your shots to him. Not only does he have an ''untelegraphed'' bullet spread attack, but he can also fire a Brimstone laser vertically across the screen with barely a second of warning. And if you think you can just run off to the side of the Haunt to dodge this, think again. Doing this causes him to charge you for a '''full heart''' of damage. And the worst part? He's a ''Cellar/Burning Basement'' boss, meaning he can potentially be the first boss encountered in a run. Some fans have come to the conclusion that he's even harder than the Widow, the previous infamous Cellar boss. And woe be to you if you encounter the champion version which fires slanted, ''bouncing'' Brimstone, forcing you to stay up close and potentially get hit by bullets. The Haunt may as well just be the new [[TheScrappy Bloat]]. What's worse is that while other bosses like the Bloat and the Matriarch were nerfed in future updates and DLCs, the Haunt was not nerfed in any way. As a matter of fact, not many of the ''Rebirth'' bosses, if ''any of them'', were nerfed at all, including the ones listed below.

* The Haunt. Initially, he's completely invincible and relies on his three [[DemonicSpiders smaller ghosts]] to assist him, but once they're killed, he starts his attacks. The Haunt is actually very fast once he starts attacking, making it difficult to lead your shots to him. Not only does he have an ''untelegraphed'' bullet spread attack, but he can also fire a Brimstone laser vertically across the screen with barely a second of warning. And if you think you can just run off to the side of the Haunt to dodge this, think again. Doing this causes him to charge you for a '''full heart''' of damage. And the worst part? He's a ''Cellar/Burning Basement'' boss, meaning he can potentially be the first boss encountered in a run. Some fans have come to the conclusion that he's even harder than the Widow, the previous infamous Cellar boss. And woe be to you if you encounter the champion version which fires slanted, ''bouncing'' Brimstone, forcing you to stay up close and potentially get hit by bullets.
* The Adversary, which is the posthumous version of the Dark One. The one and only thing that stands out about the Adversary is that it [[ThatOneAttack fires a Brimstone laser that]] ''[[AlwaysAccurateAttack homes in on you]]''. Unless you run behind the Adversary, this ''will'' hit you. This becomes incredibly problematic if there happens to be two of them in one room, as it gives you almost no room to dodge one Adversary's laser while avoiding the other Adversary's own attacks. If the Adversary manages to wander into one of the corners, get ready to take a hit, because there’s nowhere to hide!

* While Peep himself is more of a GoddamnedBoss than this {{trope}}, the same isn't true for '''[[MemeticTroll The Bloat]]'''. There are very good reasons for why he used to provide the page image. And why he has [[https://www.reddit.com/r/FUCKBLOAT/ his own Subreddit]] where the community dedicates themselves to LoveToHate him: As the [[BackFromTheDead posthumous version]] of [[KevLard Peep]], Bloat has the same amount of health as him, and shares most of his same strategy. However, unlike all versions of Peep[[note]]sans his dark cyan champion variant[[/note]], the eyes detach at the start, not [[TurnsRed after taking enough damage]]. He also shares the same attack pattern, with one notable and ''extremely hated'' exception; if the Bloat is idle and you so much as graze the area directly to the sides or in front of him, he'll [[ThatOneAttack fire Brimstone beams from his eyes]] (either two forward or one to each side). This attack is not telegraphed, and will hit you unless you've got enough speed to run past him in the split second between the trigger and firing. It's possible to get hit ''[[TheComputerIsACheatingBastard the same second you enter the room]]'' with this boss! The only safe place you can attack from is behind him, but this can't always be done as: his eyes can be behind him, he can leak out red creep behind him (which hurts you unless you have flight), and he sometimes changes position. His green champion version will also send out a spray of Ipecac bombs towards you whenever he jumps, and [[FlunkyBoss he]] can spawn [[GoddamnedBats Chargers]] when he creates damaging creep. It is also possible to fight him in both Necropolis and chapter 4 on the same run and, in Greed, the Boss switch might pit you with '''two of them'''. He's even worse in an ''Afterbirth†'' challenge called "[[https://bindingofisaacrebirth.gamepedia.com/Aprils_Fool April's Fool]]", on which '''''[[RecurringBoss every boss on every floor is The Bloat]]''''', even the final boss in the Womb! You can thank [[https://www.reddit.com/r/bindingofisaac/comments/5mbnqs/i_got_banned_from_rfuckbloat_for_coming_up_with/ this user on Reddit]] for coming up with this challenge. Granted, due to the wacky mechanics of the trial, it's functionally impossible to die, but that doesn't make it any less obnoxious. Also fortunate is that this expansion introduced the Analog Stick item, which allows you to fire diagonally and mitigates some of the difficulty if you happen to get it.

* Most of the final bosses are pretty hard, but fair once you get the hang of them, largely due to the items you might have. As [[CloseRangeCombatant Azazel]], though? They can become '''BRUTAL'''. Most of them are largely thanks to BulletHell making his close range a big problem, with big mentions going to Mom's Heart/It Lives, Isaac, ???, Mega Satan, Hush, and [[TrueFinalBoss Delirium]]; of the final two, the former even has ??? as a placeholder boss before its battle, and a boatload of health and damage resistance that ensures [[MarathonBoss it will take a long while]], while the latter dies more quickly due to lack of damage resistance, but its attacks become faster as it loses health. As for Satan, The Fallen at the start of his fight is grueling to ward off, and makes it hard to get to the true battle with Satan without suffering much damage; Satan himself is no slouch either, as although his first phase isn't too terrible, the second phase pits you with [[DemonicSpiders Kamikaze Leeches]] along with his stomp attacks.

* Death, the final Horseman, is able to summon Scythes that home in on you. It's limited homing, but they are big and hard to dodge. He can also slow you down with an Hourglass effect, making it harder for you to avoid his Scythes (and, if you're unlucky enough to face him alongside another boss in Boss Rush or War in Mega Satan's fight, the other boss' attacks, too). After you've damaged him enough, his mount detaches with its own health and charges endlessly, even ''after you've killed him''. On top of that, he spawns [[GoddamnedBats Knights]].

* Gurdy Jr. doesn't look tough, right? ''Think again.'' After summoning Pooters and/or firing eight bullets around her, she [[ThatOneAttack charges at you at a ridiculous speed with ridiculous accuracy]]. And if she misses, she might just do a little homing slide into you. After losing half health, this will be her only attack she'll do. Only bombs or slowing tears will fend off her charge attack. One of her Champion variations has two of them battle you at the same time, and they will only charge at you, only making her that much harder to defeat. ''Rebirth''[='=]s Double Trouble mechanic can actually saddle you with ''four of these gals at once''! Thankfully, unlike "her evolved form" Gurdy, Gurdy Jr. only has decent health.
* Carrion Queen, the posthumous version of Chub, can be somewhat difficult not because the boss herself is strong, but because she leaves behind damaging red poop that quickly regenerates if destroyed. On top of that, much like Scolex, only her end segment is vulnerable to attack (though getting her to [[FeedItABomb swallow bombs]] works, too). If you don't damage her fast enough to trigger her second phase, the arena will be a minefield... not that her second phase is much better, since she starts erratically bouncing around the room at high speed and can no longer be fed bombs, making it an utter pain to take off her last sliver of health, as her rapid diagonal movement makes her weak spot incredibly hard to hit. The champion version is actually better, because she instead poops out tiny heart enemies which are easy to kill and deal damage to her on death, and she doesn't enrage at low health. She's both a blessing and a curse during the BossRush, in which her poop can blend into the all the bloodstains and become hard to see, but will also cause major damage to the other bosses, potentially killing some of them ''in a few seconds''.

* While Peep himself is more of a GoddamnedBoss than this {{trope}}, the same isn't true for '''[[MemeticTroll The Bloat]]'''. There are very good reasons for why he used to provide the page image and why he has [[https://www.reddit.com/r/FUCKBLOAT/ his own Subreddit]] where the community dedicates themselves to LoveToHate him. As the [[BackFromTheDead posthumous version]] of [[KevLard Peep]], Bloat [[DamageSpongeBoss has slightly more health than him]], and shares most of his same strategy. However, unlike all versions of Peep[[note]]sans his dark cyan champion variant[[/note]], the eyes detach at the start, not [[TurnsRed after taking enough damage]]. He shares the same attack pattern, with one notable and ''extremely hated'' exception; if the Bloat is idle and you so much as graze the area directly to the sides or in front of him, he'll [[ThatOneAttack fire Brimstone beams from his eyes]] (either two forward or one to each side). This attack is not telegraphed, and will hit you unless you've got enough speed to run past the Bloat in the split second between the trigger and firing. It's possible to get hit ''[[TheComputerIsACheatingBastard the same second you enter the room]]'' with this boss! The only safe place you can attack from is behind him, but this can't always be done as: his eyes can be behind him, he can leak out red creep behind him (which hurts you), and he sometimes changes position. His Champion version will also send out a spray of Ipecac bombs towards you whenever he jumps, and [[FlunkyBoss he]] can spawn [[GoddamnedBats Chargers]] when he creates damaging creep. It is also possible to fight him in both Necropolis and chapter 4 on the same run and, in Greed, the Boss switch might pit you with '''two of them'''. He's even worse in an ''Afterbirth†'' challenge called "[[https://bindingofisaacrebirth.gamepedia.com/Aprils_Fool April's Fool]]", on which '''''[[RecurringBoss every boss on every floor is The Bloat]]''''', even the final boss in the Womb! You can thank [[https://www.reddit.com/r/bindingofisaac/comments/5mbnqs/i_got_banned_from_rfuckbloat_for_coming_up_with/ this user on Reddit]] for coming up with this challenge. Granted, due to the wacky mechanics of the trial, it's functionally impossible to die, but that doesn't make it any less obnoxious. Also fortunate is that this expansion introduced the Analog Stick item, which allows you to fire diagonally and mitigates some of the difficulty if you happen to get it.

* The Cage, which is pretty much an oversized Vis. For starters, he's the posthumous version of Mega Fatty, an already [[DamageSpongeBoss spongy boss]], and as a result has the highest health of any standard boss in the game at '''800 HP''', higher than that of any boss including ''[[DiscOneFinalBoss Mom]]'' (with the exceptions of the other final bosses). As for his choices of combat, he possesses a rolling attack that is similar to Gurdy Jr's charge but without the ability to slow the boss with knockback; only slowing tears can impede it. The real show-stopper, however, is his jump attack that sends out waves of stone that curve completely randomly and are impossible to predict. And yes, there's the chance of seeing two of them in one room in the final levels. ''Afterbirth'' introduces a pink champion version of two Cages, which can result in a Double Trouble room having ''four Cages at once''.
* Most of the final bosses are pretty hard, but fair once you get the hang of them, largely due to the items you might have. As [[CloseRangeCombatant Azazel]], though? They can become '''BRUTAL'''. Most of them are largely thanks to BulletHell making his close range a big problem, with big mentions going to Mom's Heart/It Lives, Isaac, ???, Mega Satan, Hush, and [[TrueFinalBoss Delirium]]; of the final two, the former even has ??? as a placeholder boss before its battle, and a boatload of health and damage resistance that ensures [[MarathonBoss it will take a long while]], while the latter dies more quickly due to lack of damage resistance, but its attacks become faster as it loses health. As for Satan, The Fallen at the start of his fight is grueling to ward off, and makes it hard to get to the true battle with Satan without suffering much damage; Satan himself is no slouch either, as although his first phase isn't too terrible, the second phase pits you with [[DemonicSpiders Kamikaze Leeches]] on top of his stomp attacks.

* [[BandageMummy Rag Man]], especially when encountered as your first boss. He's a first floor boss with a surprising amount of health for his small size and tends to walk away from the player, making him hard to actually hit. While his only direct attack is a line of homing bullets with short range, every so often, [[FlunkyBoss he'll detach his head and roll it]]. If you don't destroy the head, which isn't easy because it can take a lot of punishment, [[FlunkyBoss it spawns]] a [[DemonicSpiders Ragling]], a Trite variant that shoots rotating bullets. And if he's not killed quickly, he can summon up to three of them. But that's not all; Raglings spawned by Rag Man are unique in that they leave behind bandages when you kill them. If enough bandages accumulate and his health is below a third, Rag Man can instantly resurrect two or three Raglings, ''[[HealThyself healing himself]]'' in the process. All these factors can make the fight difficult. It's even worse in Greed Mode, where you might end up fighting two at once on the first floor. ''Afterbirth†'' finally nerfed him for good measure, reducing his health[[note]]from 250 HP to 200 HP[[/note]] and thus making the fight much less unfair. Unlike other bosses, however, if you find him in later floors, he becomes much more manageable.
* The Stain, the undead form of Polycephalus. Like the original, it spends most of its time underground, popping up only to attack. While this is predictable most of the time, if you don't get it to pop up before it disappears, then you have no idea where on the field it will show up. This means it can easily get in your face to use its CombatTentacles attack, which is very fast and has virtually no tell aside from the Stain appearing in front of you. That is, if it doesn't go for just popping up ''[[TeleFrag directly underneath you]]'' for unavoidable contact damage. All of this is before we talk about its [[ThatOneAttack strongest attack]]: if it pops up as a single face, it unleashes a BulletHell attack with a volume comparable to ''Mom's Heart''. Finally, Greed Mode can pit you against ''two Stains at once'', or, if you're really unlucky, '''three'''. Watch out if they all use their BulletHell attack ''[[OhCrap at the same time]]''. The fact it's a chapter 2 boss only adds insult to injury.

* If you thought the TrueFinalBoss fight against Mega Satan in ''Rebirth'' was brutal, you're far from the worst. Enter '''[[EldritchAbomination Hush]]'''. Reach Mom's Heart or It Lives and beat them in under 30 minutes to get access to its lair, a place called ???. Before the fight, the room gives you two item rooms (with two item options to choose from on each room), four golden chests, and a shop. Needless to say, ''you will need them''. You'll first face Hush as a glorified ???, but defeating it is not the end of it, as it reveals [[OneWingedAngel its true form]]. With [[SequentialBoss five phases to the true form's battle]], loads and loads of BulletHell attacks that make bosses from ''Franchise/TouhouProject'' blush (and one of which [[ThatOneAttack wraps around the room's boundaries]]), the ability to [[FlunkyBoss spawn loads and loads of enemies]] to block your shots unless you have a piercing attack, the ability to merge with the floor to completely avoid your attacks, and the [[DamageSpongeBoss second-highest HP pool]] at [[NumberOfTheBeast 6666 HP]] on top of damage resistance that scales with your current damage, you're in for [[MarathonBoss the actual longest fight in the game]], no matter your item build. It's easy to get hit by its attacks as it is, so you also better hope you came in to its battle packing a lot of health... unless you're playing as [[OneHitPointWonder The Lost]] or [[ScrappyMechanic The Keeper]], in which case... [[ThisIsGonnaSuck good luck]], '''[[NintendoHard you'll need it]]'''. Granted, you can skip this boss fight in ''Repentance'' by using IV - The Emperor?, you fight [[WarmUpBoss Monstro]] instead of Hush, and beating [[BreatherBoss him]] will count as beating Hush.

* Rag Mega! [[SarcasmMode Because Rag Man wasn't enough!]] He bounces around the room like Husk, but can periodically become invincible by wrapping himself in bandages, similar to a Host. He also has three purple orbitals surrounding him that can't be destroyed, making it even harder to hit him. As he loses a certain amount of health, he will start dispersing his orbitals, one by one, which will then follow the player (while actually making him easier to hit); if your speed is low, they will constantly harass you. On top of that, like Rag Man, Rag Mega can spawn Raglings to assist him, but thankfully, instead of reviving them on the spot, he summons several pillars of purple light that, while they can damage you, aren't guaranteed to home in on and revive any dead Ragling they come in contact with. All of this makes Rag Mega as dangerous as his inferior form, despite having pitiful health[[note]]120 HP[[/note]] compared to him. Granted, ''Repentance'' buffed bombs to make them deal 100 HP, which means that if you've got some to spare you can simply defeat him in one go.

* The Sisters Vis, an alternate form of The Cage that can appear in chapters 3 and 4. Where to begin? DualBoss? Check. [[DamageSpongeBoss High health]] (between both sisters[[note]]350 HP per sister, for a total of 700 between both[[/note]])? Check. [[FlunkyBoss Summons smaller Vis enemies]]? Check. Rolls around the arena (with the added bonus of one of them occasionally [[TurnsRed Turning Red]] and moving faster than usual)? Check. Surviving sister TurnsRed if you kill one of them? Check. [[WaveMotionGun Gigantic Brimstone laser]] that can ocasionally wave back and forth with an enormous amount of coverage if only one of them fires it? ''[[ThatOneAttack Dear God check]].'' Their health even used to be higher, before updates considerably nerfed it[[note]]first from 800 HP to 500 HP per sister, then to 350 HP per sister[[/note]]. As an added bonus, in Greedier mode, you may find yourself fighting ''eight of them at once''! Good luck, you're gonna need it!
* This expansion introduced a black champion version of Brownie that spawns ''Drowned Chargers'' instead of Corn Dips. Unless you're very powerful already, the amount of enemies on top of Brownie's BulletHell will quickly become overwhelming. Champion Brownie was nerfed in a post-release patch to only spawn normal Chargers, but remains formidable thanks to the [[ZergRush sheer quantity of Chargers produced.]]

* Bumbino's attacks are aplenty and fairly unpredictable, not helped by the arena you will be pitted in. The room will always be full of rocks, which will do nothing to protect you, as he will always break them out of his way. His dash attack covers an excellent range and is also very fast, and makes rocks rain all over the battlefield, so even if he leaves himself open afterwards, you will not have much time to get some counterhits. His swipe attacks also [[BanditMook cause you to lose coins, which he will take for himself]] and will not be replenished when he's defeated - he prioritizes getting the coins before attacking you, too. He can also throw a bomb at you, much like he can do so when he's a familiar. Finally, all of his attacks deal one full heart of damage, so if you're not careful, you're going to lose lots of health to this boss. By the way, this is only in chapter 2, and he can appear in all of its environments.

** Ultra Death has no second phase like the other three Horsemen, but his summons are numerous. Between three waves of 11 Death Scythes that soak up a lot of hits, followed by near-indestructible, Ultra Death Heads that [[ZergRush fill the screen completely]], seeing your health drop rapidly isn't unheard of. And after that, Death will destroy the Death Heads to black the screen out and slash and hack at you with his scythe. The only tell you'll have is his grunt and his [[RedEyesTakeWarning red, Terminator-esque eye]] amidst the black mist, and you will need very fast reflexes to keep dodging.

* Colostomia. Not only winning [[NauseaFuel the most disgusting boss]] in ''Repentance'' yet she's also one of the hardest. On top of being [[DamageSpongeBoss an already tanky boss]][[note]]380 HP[[/note]] (even tankier than the Basement's Dangle), all of her attacks are dangerous. She slides around really fast, leaving explosive gas clouds which react to bomb explosions. She also fires out butt bombs that detonate these same gas clouds, on top of the explosions having [[HitboxDissonance varying range to their size]]. Unless you pay attention to the gas the charge leaves behind, you won't have a tell at all. When low on health, Colostomia will shed her "armor" and change her scheme, starting to spew out the bombs while jumping around and leaving gas clouds and brown creep that, unlike other types of the same creep, hurts you. And here's the worst part: this is only in chapter 1! Thank goodness she only appears in, fittingly enough, [[SewerLevel Dross]].
* Hornfel, from the Mines. This bugger tends to use hit and run methods to kill you. And they are nearly all explosive (with one exception though that comes ''after'' he pelts bombs like a maniac) so unless you have great reflexes and speed, or defensive items like the Wafer, or something that makes you immune to explosives like Host Hat, you're going to lose a ton of hearts (or runs) from him. By the way, remember his attack where he sends dummies of himself in ''Antibirth''? It was ''buffed'' to include three now. All with bombs if you hit one by mistake. Prepare to rage, especially if you are playing any version of the Lost!

* The Scourge is the KingMook to [[DemonicSpiders the Whipper and Cultist families]]. Sounds painful enough? '''''Because it is!''''' While its green multi-projectile attack is a fairer one to dodge (even if it spawns [[TheGoomba Small Maggots]]), it also makes a lot of use of its tendrils to [[WhipItGood lash at you]] and the walls. It has three variations to this attack: lashing one at you and dragging it at the wall to fire projectiles and maggots, firing one at you and another at the wall then rotate them while firing rings of projectiles, or embedding both at the wall while indulging in BulletHell. And no, you can't leave the area you are in if it corners you; the tendrils are solid, so you ''will'' have to survive the projectile storm. And lastly, it hovers to the center of the room while sucking you and streams of shots in, often changing the directions of the streams, meaning that you'll have to backtrack in order to not get cornered. To boot? The Scourge has [[DamageSpongeBoss a colossal amount of HP]][[note]]950 HP, which is that of ''Mom's Heart''[=/=]''It Lives''[[/note]], so you will stay a very long while either [[MarathonBoss trying to outlast this hellspawn]], or [[HaveANiceDeath die trying]].
* Mother, the renamed Witness, is far more of a threat than in ''Antibirth''. For one thing, you don't have a lot of room to work with compared to ''Antibirth'' making dodging her attacks far more difficult. She also doesn't have a health bar and has a crapload of health to boot. And the attacks themselves include summoning a crapload of gapers that take up a lot of space in the already small room walking up to her and her hitting towards you. The worst one though has to be when she pukes out a Fistula and smacks it around with bullets (and if you live then the pieces of it.) going everywhere. And that's just phase 1. Phase 2 begins after shooting a laser out of nowhere and then coming out to fight you the same way she did in ''Antibirth''. She doesn't move around much but she's also blocking off a good part of the room. Her attacks include jumping up and charging before crashing down in the center sending shockwaves and her sucking bullets up to them spit out at you. [[SarcasmMode Have fun with the Tainted characters]], especially [[OneHitPointWonder The Lost]] and [[TierInducedScrappy Jacob]]!

'''Note:''' {{Final Boss}}es and [[WakeUpCallBoss Wake-Up Call Bosses]] aren't allowed unless they are overtly hard by their standards. Also, all {{spoiler}}s are [[Administrivia/SpoilersOff unmarked]]! '''Administrivia/YouHaveBeenWarned!'''

'''Note:''' {{Final Boss}}es and [[WakeUpCall Wake-Up Call Bosses]] aren't allowed unless they are overtly hard by their standards. Also, all {{spoiler}}s are [[Administrivia/SpoilersOff unmarked]]! '''Administrivia/YouHaveBeenWarned!'''

* Most of the final bosses are pretty hard, but fair once you get the hang of them, largely due to the items you might have. As [[GlassCannon Aza]][[CloseRangeCombatant zel]], though? They can become '''BRUTAL'''. Most of them are largely thanks to BulletHell making his close range a big problem, with big mentions going to Mom's Heart/It Lives, Isaac, ???, Mega Satan, Hush, and [[TrueFinalBoss Delirium]]; of the final two, the former even has ??? as a placeholder boss before its battle, and a boatload of health and damage resistance that ensures [[MarathonBoss it will take a long while]], while the latter dies more quickly due to lack of damage resistance, but its attacks become faster as it loses health. As for Satan, The Fallen at the start of his fight is grueling to ward off, and makes it hard to get to the true battle with Satan without suffering much damage; Satan himself is no slouch either, as although his first phase isn't too terrible, the second phase pits you with [[DemonicSpiders Kamikaze Leeches]] on top of his stomp attacks.

* While Peep himself is more of a GoddamnedBoss than this {{trope}}, the same isn't true for '''[[MemeticTroll The Bloat]]'''. There are very good reasons for why he used to provide the page image and why he has [[https://www.reddit.com/r/FUCKBLOAT/ his own Subreddit]] where the community dedicates themselves to LoveToHate him. As the [[BackFromTheDead posthumous version]] of [[KevLard Peep]], Bloat [[DamageSpongeBoss has slightly more health than him]], and shares most of his same strategy. However, unlike all versions of Peep[[note]]sans his dark cyan champion variant[[/note]], the eyes detach at the start, not [[TurnsRed after taking enough damage]]. He shares the same attack pattern, with one notable and ''extremely hated'' exception; if the Bloat is idle and you so much as graze the area directly to the sides or in front of him, he'll [[ThatOneAttack fire Brimstone beams from his eyes]] (either two forward or one to each side). This attack is not telegraphed, and will hit you unless you've got enough speed to run past the Bloat in the split second between the trigger and firing. It's possible to get hit ''[[TheComputerIsACheatingBastard the same second you enter the room]]'' with this boss! The only safe place you can attack from is behind him, but this can't always be done as: his eyes can be behind him, he can leak out red creep behind him (which hurts you), and he sometimes changes position. His Champion version will also send out a spray of Ipecac bombs towards you whenever he jumps, and c[[FlunkyBoss he]] can spawn [[GoddamnedBats Chargers]] when he creates damaging creep. It is also possible to fight him in both Necropolis and chapter 4 on the same run and, in Greed, the Boss switch might pit you with '''two of them'''. He's even worse in an ''Afterbirth†'' challenge called "[[https://bindingofisaacrebirth.gamepedia.com/Aprils_Fool April's Fool]]", on which '''''[[RecurringBoss every boss on every floor is The Bloat]]''''', even the final boss in the Womb! You can thank [[https://www.reddit.com/r/bindingofisaac/comments/5mbnqs/i_got_banned_from_rfuckbloat_for_coming_up_with/ this user on Reddit]] for coming up with this challenge. Granted, due to the wacky mechanics of the trial, it's functionally impossible to die, but that doesn't make it any less obnoxious. Also fortunate is that this expansion introduced the Analog Stick item, which allows you to fire diagonally and mitigates some of the difficulty if you happen to get it.

'''Beware of [[Administrivia/SpoilersOff spoilers]]!'''

* The Mask of Infamy, a [[GiantMook giant copy of the mask-heart enemies]]. Its AI is [[ArtificialBrilliance a lot better than the mooks it takes from]] (not that they were not smart before), and ''both'' the mask and heart need to be killed. The mask can only be hit from behind, and has near-perfect turning reflexes, making the already annoying CatAndMouseBoss harder. If you don't have a piercing attack, bomb tears or enough bombs, expect to spend a long time fighting.
* '''[[MemeticTroll The Bloat]]'''. This guy has very good reasons for why he has [[https://www.reddit.com/r/FUCKBLOAT/ his own Subreddit]] where the community dedicates themselves to LoveToHate it. As the [[BackFromTheDead posthumous version]] of Peep, Bloat has slightly more health than him, and shares most of his same strategy. However, the eyes detach at the start, not after taking enough damage like Peep does. He shares the same attack pattern, with one notable and ''extremely hated'' exception; if the Bloat is idle and you so much as graze the area directly to the sides or in front of him, he'll [[ThatOneAttack fire Brimstone beams from his eyes]] (either two forward or one to each side). This attack is not telegraphed, and will hit you unless you've got enough speed to run past the Bloat in the split second between the trigger and firing. It's possible to get hit ''[[TheComputerIsACheatingBastard the same second you enter the room]]'' with this boss! The only safe place you can attack from is behind him, and his eyes always seem to be behind him. His Champion version will also send out a spray of Ipecac bombs towards you whenever he jumps, and can spawn [[GoddamnedBats Chargers]] when he creates damaging creep. It is also possible to fight him in both Necropolis and chapter 4 on the same run and, in Greed, the Boss switch might pit you with '''two of them'''. Wherever you go, be sure to always have more than enough health in case he turns up unannounced, especially in The Chest or Dark Room.
** Afterbirth† has a challenge called "[[https://bindingofisaacrebirth.gamepedia.com/Aprils_Fool April's Fool]]", on which '''''[[RecurringBoss every boss on every floor is The Bloat]]''''', even the final boss in the Womb! You can thank [[https://www.reddit.com/r/bindingofisaac/comments/5mbnqs/i_got_banned_from_rfuckbloat_for_coming_up_with/ this user on Reddit]] for coming up with this challenge. On the plus side, due to the wacky mechanics of the trial, it's functionally impossible to die, but that doesn't make it any less obnoxious. Also fortunate is that this expansion introduced the Analog Stick item, which allows you to fire diagonally and mitigates some of the difficulty if you happen to get it.
* Conquest, the new horseman in ''Wrath of the Lamb'', has a charge which covers almost the entire screen, which can be impossible to dodge if you're too slow or get trapped too far from the safe area. There's little warning for his fast-moving homing bullets, and the beams he releases from the sky are impossible to dodge by your own ability (unless you have flight), you just have to hope they don't target you. His AI sometimes has a small pathfinding bug where he slowly drifts into a corner and into the wall where normal tears can't hit, while he can simply teleport off screen to do more damage to you. Combine that with his whole heart damage for everything he does and Conquest can end your game. Conquest's game plan is mostly teleporting, so rush attacks (Game Kid, Unicorn, The Chariot) are much less useful than with most bosses. To make it worse, while Conquest can usually only replace Death, due to a glitch in ''Wrath of the Lamb'', he can also randomly replace [[BreatherBoss War]], who is fought two floors earlier (though thankfully this is no longer the case as of ''Rebirth'' and its expansions). And in ''Repentance'', his sky beams attack was made easier to telegraph, but [[MagicMissileStorm many more beams rain down on the battlefield]], [[TookALevelInBadass making the attack overall that much harder to dodge]].

* The Haunt. At first, he's completely invincible and relies on his three [[DemonicSpiders smaller ghosts]] to assist him, but once they're killed, he starts his attacks. The Haunt is actually very fast once he starts attacking, making it difficult to lead your shots to him. Not only does he have an ''untelegraphed'' bullet spread attack, but he can also fire a Brimstone laser vertically across the screen with barely a second of warning. And if you think you can just run off to the side of the Haunt to dodge this, think again. Doing this causes him to charge you for a '''full heart''' of damage. And the worst part? He's a ''Cellar/Burning Basement'' boss, meaning he can potentially be the first boss encountered in a run. Some fans have come to the conclusion that he's even harder than the Widow, the previous infamous Cellar boss. And woe be to you if you encounter the champion version which fires slanted, ''bouncing'' Brimstone, forcing you to stay up close and potentially get hit by bullets.

* [[BandageMummy Rag Man]], especially when encountered as your first boss. He's a first floor boss with a surprising amount of health for his small size and tends to walk away from the player, making him hard to actually hit. While his only direct attack is a line of homing bullets with short range, every so often, [[FlunkyBoss he'll detach his head and roll it]]. If you don't destroy the head, which isn't easy because it can take a lot of punishment, [[MookMaker it spawns a]] [[DemonicSpiders Ragling]], a Trite variant that shoots rotating bullets. And if he's not killed quickly, he can summon up to three of them. But that's not all; Raglings spawned by Rag Man are unique in that they leave behind bandages when you kill them. If enough bandages accumulate and his health is below a third, Rag Man can instantly resurrect two or three Raglings, ''[[HealThyself healing himself]]'' in the process. All these factors can make the fight difficult. It's even worse in Greed Mode, where you might end up fighting two at once on the first floor. ''Afterbirth†'' finally nerfed him for good measure, reducing his health[[note]]from 250 HP to 200 HP[[/note]] and thus making the fight much less unfair. Unlike other bosses, however, if you find him in later floors, he becomes much more manageable.

* If you thought the TrueFinalBoss fight against Mega Satan in ''Rebirth'' was brutal, you're far from the worst. Enter '''[[EldritchAbomination Hush]]'''. Reach Mom's Heart or It Lives and beat them in under 30 minutes to get access to its lair, a place called ???. Before the fight, the room gives you two item rooms (with two item options to choose from on each room), four golden chests, and a shop. Needless to say, ''you will need them''. You'll first face Hush as a glorified ???, but defeating it is not the end of it, as it reveals [[OneWingedAngel its true form]]. With [[SequentialBoss five phases to the true form's battle]], loads and loads of BulletHell attacks that make bosses from ''Franchise/TouhouProject'' blush (and one of which [[ThatOneAttack wraps around the room's boundaries]]), the ability to [[FlunkyBoss spawn loads and loads of enemies]] to block your shots unless you have a piercing attack, the ability to merge with the floor to completely avoid your attacks, and the [[DamageSpongeBoss second-highest HP pool]] at [[NumberOfTheBeast 6666 HP]] on top of damage resistance that scales with your current damage, you're in for [[MarathonBoss the actual longest fight in the game]], no matter your item build. It's easy to get hit by its attacks as it is, so you also better hope you came in to its battle packing a lot of health... unless you're playing as [[OneHitPointWonder The Lost]] or [[ScrappyMechanic The Keeper]], in which case... [[ThisIsGonnaSuck good luck]], '''[[NintendoHard you'll need it]]'''.
** You can skip this boss fight in ''Repentance'' by using IV - The Emperor?, you fight Monstro instead of Hush, and beating him will count as beating Hush.

* [[TookALevelInBadass Rag Mega!]] [[SarcasmMode Because Rag Man wasn't enough!]] He bounces around the room like Husk, but can periodically become invincible by wrapping himself in bandages, similar to a Host. He also has three purple orbitals surrounding him that can't be destroyed, making it even harder to hit him. As he loses a certain amount of health, he will start dispersing his orbitals, one by one, which will then follow the player (while actually making him easier to hit); if your speed is low, they will constantly harass you. On top of that, like Rag Man, Rag Mega can spawn Raglings to assist him, but thankfully, instead of reviving them on the spot, he summons several pillars of purple light that, while they can damage you, aren't guaranteed to home in on and revive any dead Ragling they come in contact with. All of this makes Rag Mega as dangerous as his inferior form, despite having pitiful health[[note]]120 HP[[/note]] compared to him.
** ''Repentance'' buffed bombs to make them deal 100 HP, which means that if you've got some to spare, you ''should'' go for it as after a few shots, you'll simply defeat him in one go.
* Damage resistance, although [[ScrappyMechanic a controversial mechanic as a whole due to how it works]], is generally accepted because the only bosses that have it in ''Afterbirth'' are "superbosses". ''Afterbirth†'' breaks this rule with Big Horn, a Catacombs DamageSpongeBoss who will usually take the same amount of time to kill no matter where you fight him. The only way to deal decent damage is via FeedItABomb, but it's hard to pull off. His other tricks include tossing many varieties of bombs (all of which deal a full heart of damage), trying to corner you with slapping hands, and [[MookMaker summoning a weakened]] [[DegradedBoss Little Horn]]. An update quickly reduced his health [[note]]from 600 HP to 480 HP[[/note]] and gave his attacks a little more delay, whereas one released a month later (most importantly) removed his damage resistance. His Little Horn summon also got reworked in ''Repentance'' so that you no longer have to fight it alongside Big Horn. Nevertheless, despite these changes, [[GoddamnedBoss he can still be quite painful to fight]].

* Thought that bosses like The Bloat, The Adversary, The Cage, or Sisters Vis were painful? The Forgotten update adds The Matriarch, an unholy mix between Fistula, Chub, and the Chubber and Fistuloid enemies that's [[DamageSpongeBoss even sturdier]][[note]]at 700 HP[[/note]], and who can appear on ''any'' environment of the Womb (but as of ''Repentance'', appears most commonly in the Scarred Womb). The Matriarch shoots Chargers in the eight cardinal directions, spawns Fistuloids that surround her, and shoots a jumbo tear that leaves a puddle of toxic blood creep. As she takes damage, she sheds small Fistulas and Fistuloids which shoot Chargers like Chubber does. At medium health, she starts summoning [[ZergRush an enormous wave of Fistuloids that immediatly shoot their Chargers at you]]. When "killed", the Chub sheds her Fistula armor completely, spawning even more Chargers, Fistulas and Fistuloids. Lastly, unlike the normal version of Chub, this one [[DefiedTrope defies]] the FeedItABomb strategy by [[HoistByHisOwnPetard spitting it back at]] [[NoYou you]]; only The Forgotten can avoid this attack by [[TennisBoss swinging the bomb back at her]] with his bone. It's virtually impossible to avoid getting hit simply because the Matriarch is big enough, her spawns are numerous enough, and her attacks are quick enough, that there is just nowhere in the room you can hide. As a result, to many, this boss became the new Bloat for the final days of ''Afterbirth†'', being considered ''even'' harder than the non-tankiest final bosses in the game, and unlike bosses like Sisters Vis and Big Horn, was never nerfed - it took until ''Repentance'' where this hellspawn was '''''finally''''' {{nerf}}ed, causing her to [[CastFromHitPoints take 30 HP of damage when she summons a Fistuloid]], making the Fistuloids that orbit her attack less aggressively, and shedding less pieces of Fistula armor whenever her health is reduced a certain amount - nevertheless, she's remains a potentially very dangerous boss.
* '''Delirium'''. In addition to having an absolutely titanic amount of HP,[[note]]10,000, the highest HP of any enemy tied with The Beast[[/note]] its attacks are hard to dodge as they are, with very convoluted and tight patterns of bullets fired with barely any downtime, some of which can be ipecac shots. No matter what Delirium transforms into, though, expect to be annoyed by his propensity to teleport around the room at random (often [[TeleFrag right besides you]]) and the fact that he gets faster as his health gets lower. Even so, the amount and type of bosses that you encounter, combined with the [[GameBreaker build you amassed before the fight]], are what will make Delirium either a boss whose forms are [[CurbStompBattle only a nuisance while dealing with its bullet patterns]], or a [[NintendoHard true nightmare of a boss that]] [[MarathonBoss you'll have to outlast]]. It doesn't help that the level you find Delirium in, [[MarathonLevel The Void]], has [[GoddamnedBats enemies]] [[DemonicSpiders of all types]] that will cause you to hope you can hold onto your life, as well as bosses that Delirium can transform into during the fight... yes, that includes all and each of the other bosses on this page (up to ''Afterbirth†'') [[note]]except for Hush, unless you encounter ''very'' few bosses throughout your run[[/note]]. It gets to the point where most consider it even harder than '''The Beast''', ''Repentance'''s TrueFinalBoss.

[[folder: ''Repentance'']]

* The alternate path's Mom is [[TookALevelInBadass much more deadly than her Depths counterpart]]. Her monster summons include Psychic Horfs, [[DemonicSpiders Raglings]] and Cursed Globins which are much more deadly than the Depths could ever be. If you face her in the alternate floor, [[ThatOneLevel Gehenna]], you'll also have to contend with that floor's DemonicSpiders as well. Her "safe" eye will now a fire twin Brimstone laser you are in sight. And finally, her stomp has a chance to instead be three quick stomps, with the third one [[ThatOneAttack leaving rows of explosions in four directions that can't be blocked by Host Hat or Pyromaniac]], because why not? The good thing is that she will never use her had attack, and that she can't stomp the ground thrice if she's firing her Brimstone, and viceversa. However, if there was a time to use the Bible, then now would be the time.

* [[TookALevelInBadass Mother, the renamed Witness]], is far more of a threat than in ''Antibirth''. For one thing, you don't have a lot of room to work with compared to ''Antibirth'' making dodging her attacks far more difficult. She also doesn't have a health bar and has a crapload of health to boot. And the attacks themselves include summoning a crapload of gapers that take up a lot of space in the already small room walking up to her and her hitting towards you. The worst one though has to be when she pukes out a Fistula and smacks it around with bullets (and if you live then the pieces of it.) going everywhere. And that's just phase 1. Phase 2 begins after shooting a laser out of nowhere and then coming out to fight you the same way she did in ''Antibirth''. She doesn't move around much but she's also blocking off a good part of the room. Her attacks include jumping up and charging before crashing down in the center sending shockwaves and her sucking bullets up to them spit out at you. Have fun with the Tainted characters, especially The Lost and Jacob!

* Pestilence is mostly a pain because of room design more than anything else. Fortunately, his ipecac blasts will clear the rocks out eventually. Unfortunately, he is spawning grubs all over, and sometimes rapid fires his ipecac blasts which also cover the floor in toxic green spots. Once you get to his second stage, it is easy... but good luck getting to his second stage on more than a heart or two. He's even worse in ''Rebirth'', as his ipecac blasts are faster.
* Death, the final Horseman, is able to summon Scythes that home in on you. It's limited homing, but they are huge and hard to dodge. After you've damaged him enough, his mount detaches with its own health and charges endlessly, even ''after you've killed him''. On top of that, he spawns [[GoddamnedBats Knights]].
* The Headless Horseman is a DualBoss. The body shoots bombs constantly, while the head shoots bullets with almost no warning and charges frequently. The charges will cover top, middle, and bottom, and not always in the same order. The head also appears as a DegradedBoss, sometimes more than one at a time. What's even worse is that this guy has potential to be the very first boss in a run.
* The Fallen can be difficult if encountered [[EarlyBirdBoss early in the game]] or when damage output is low. It attacks primarily with fast, spreading bullets fired in rapid succession and by chasing the player around, always followed by a four-way brimstone blast. The real kicker comes when it splits into two, smaller copies upon reaching half health. The copies act independently, resulting in bullet and brimstone hell and can quickly ruin your run if you don't take at least one of them out quickly. ''Rebirth'' thankfully nerfed The Fallen by giving it scaling HP, making it weaker on early floors.

* Ultra Pride is a DualBoss. The main boss ([[CreatorCameo Edmund]]) always does one full heart of damage without the Wafer and has an attack where he spontaneously creates a giant poison stream in front of him with long range. Then there's the familiar (Florian), who behaves like the Babies, meaning that he can teleport. In addition, he fires fast moving, long-range ''homing'' bullets; the exact same type fired by Isaac and ???. Also unfortunate is that, if you're going for Platinum God, you must defeat Ultra Pride at least once.
* The Blighted Ovum, Gemini's [[BackFromTheDead posthumous version]]. As with Gemini, Contusion periodically charges at the player at a faster speed. Unlike Gemini, Contusion doesn't need to catch his breath between rounds, and leaves behind a lethal blood trail that deals '''a full heart of health in damage''', and sticks around for just enough time that you will likely step on it after completing a circle around the room. What about Suture? Fortunately, he's dead, so you don't have to hit him. Unfortunately, [[ThatOneAttack he shoots Brimstone lasers]] if he makes eye contact with you. The only saving grace for the Blighted Ovum is that you only need to kill Contusion, meaning he has less health than Gemini. ''Rebirth'' also toned him down by causing his blood trail to deal only half a heart of damage. Still, if you can't kill Contusion quickly by then, and you lack flight, you are very screwed.
* Gurdy Jr. doesn't look tough, right? Think again. After summoning Pooters and/or firing eight bullets around her, she [[ThatOneAttack charges at you at a ridiculous speed with ridiculous accuracy]]. And if she misses, she might just do a little homing slide into you. After losing half health, this will be her only attack she'll do. Only bombs or slowing tears will fend off her charge attack. One of her Champion variations has two of them battle you at the same time, and they will only charge at you, only making her that much harder to defeat. ''Rebirth''[='=]s Double Trouble mechanic can actually saddle you with ''four of these gals at once''! Thankfully, unlike "her mother" Gurdy, Gurdy Jr. only has decent health.
* Carrion Queen, the posthumous version of Chub, can be somewhat difficult not because the boss herself is strong, but because she leaves behind damaging red poop that quickly regenerates if destroyed. On top of that, much like Scolex, only her end segment is vulnerable to attack (though getting her to [[FeedItABomb swallow bombs]] works, too). If you don't damage her fast enough to trigger her second phase, the arena will be a minefield… not that her second phase is much better, since she starts erratically bouncing around the room at high speed and can no longer be fed bombs, making it an utter pain to take off her last sliver of health, as her rapid diagonal movement makes her weak spot incredibly hard to hit. The champion version is actually better, because she instead poops out tiny heart enemies which are easy to kill and doesn't enrage at low health. She's both a blessing and a curse during the {{boss rush}}, in which her poop can blend into the all the bloodstains and become hard to see, but will also cause major damage to the other bosses, potentially killing them ''in a few seconds''.
* The Mask of Infamy, a [[GiantMook giant copy of the mask-heart enemies]]. Its AI is [[ArtificialBrilliance a lot better than the mooks it takes from]] (not that they were not smart before), and ''both'' the mask and heart need to be killed. The mask can only be hit from behind, and has near-perfect turning reflexes. If you don't have a piercing attack, expect to spend a long time fighting.
* '''[[MemeticTroll The Bloat]]'''. This guy has very good reasons for why [[TheScrappy he is hated so much]] by the community, and even has [[https://www.reddit.com/r/FUCKBLOAT/ his own Subreddit]]. As the [[BackFromTheDead posthumous version]] of Peep, it has slightly more health than him, and shares most of its same strategy. However, the eyes detach at the start, not after taking enough damage like Peep does. It shares the same attack pattern, with one notable and ''extremely hated'' exception; if the Bloat is idle and you so much as graze the area directly to the sides or in front of him, he'll fire Brimstone beams from his eyes (either two forward or one to each side). This attack is not telegraphed, and will hit you unless you've got enough speed to run past the Bloat in the split second between the trigger and firing. It's possible to get hit ''[[TheComputerIsACheatingBastard the same second you enter the room]]'' with this boss! The only safe place you can attack from is behind him, and his eyes always seem to be behind him. Its Champion version will also send out a spray of Ipecac bombs towards you whenever he jumps, and can spawn [[GoddamnedBats Chargers]] when it creates damaging blood. It is also possible to fight him in both Necropolis and Utero on the same run and, in Greed, the Boss switch might pit you with '''two of them'''. Wherever you go, be sure to always have more than one heart in case he turns up unannounced, especially in The Chest or Dark Room.
** Afterbirth+ has a challenge called "[[https://bindingofisaacrebirth.gamepedia.com/Aprils_Fool April's Fool]]", on which '''''every boss on every floor is The Bloat''''', even the final boss in the Womb! You can thank [[https://www.reddit.com/r/bindingofisaac/comments/5mbnqs/i_got_banned_from_rfuckbloat_for_coming_up_with/ this user on Reddit]] for coming up with this challenge. On the plus side, due to the wacky mechanics of the trial, it's functionally impossible to die, but that doesn't make it any less obnoxious. Also fortunate is that this expansion introduced the Analog Stick item, which allows you to fire diagonally and mitigates some of the difficulty if you happen to get it.
* Conquest, the new horseman in ''Wrath of the Lamb'', has a charge which covers almost the entire screen, which can be impossible to dodge if you're too slow or get trapped too far from the safe area. There's little warning for his fast-moving homing bullets, and the beams he releases from the sky are impossible to dodge by your own ability (unless you have flight), you just have to hope they don't hit you. His AI sometimes has a small pathfinding bug where he slowly drifts into a corner and into the wall where normal tears can't hit, while he can simply teleport off screen to do more damage to you. Combine that with his whole heart damage for everything he does and Conquest can end your game. Conquest's game plan is mostly teleporting, so rush attacks (Game Kid, Unicorn, The Chariot) are much less useful than with most bosses. To make it worse, while Conquest can usually only replace Death, due to a glitch, he can also randomly replace [[BreatherBoss War]], who is fought two floors earlier.

[[folder:''Rebirth'']]

* The Adversary, which is the posthumous version of the Dark One. The one and only thing that stands out about the Adversary is that it fires a Brimstone laser that ''[[AlwaysAccurateAttack homes in on you]]''. Unless you run behind the Adversary, this ''will'' hit you. This becomes incredibly problematic if there happens to be two of them in one room, as it gives you almost no room to dodge one Adversary's laser while avoiding the other Adversary's own attacks. If the Adversary manages to wander into one of the corners, get ready to take a hit, because there’s nowhere to hide!

[[/folder]]
[[folder: ''Afterbirth'', ''Afterbirth†'']]

* [[BandageMummy Rag Man]], especially when encountered as your first boss. He's a first floor boss with a surprising amount of health for his small size and tends to walk away from the player, making him hard to actually hit. While his only direct attack is a line of homing bullets with short range, every so often, [[FlunkyBoss he'll detach his head and roll it]]. If you don't destroy the head, which isn't easy because it can take a lot of punishment, [[MookMaker it spawns a]] [[DemonicSpiders Ragling]], a Trite variant that shoots rotating bullets. And if he's not killed quickly, he can summon up to three of them. But that's not all; Raglings spawned by Rag Man are unique in that they leave behind bandages when you kill them. If enough bandages accumulate and his health is below a third, Rag Man can instantly resurrect two or three Raglings, ''[[HealThyself healing himself]]'' in the process. All these factors can make the fight difficult. It's even worse in Greed Mode, where you might end up fighting two at once on the first floor. Afterbirth† finally nerfed him for good measure, reducing his health[[note]]from 250 HP to 200 HP[[/note]] and thus making the fight much less unfair. Unlike other bosses, however, if you find him in later floors, he becomes much more manageable.
* The red champion version of Mega Fatty. Not only does he still have his quick stomp, said attack now shoots bullets in all directions when he lands (which will generally be right next to you). On top of that, he has a second dangerous attack: instead of the regular version's easily-dodgeable WaterfallPuke, he follows up his "sucking in everything in the room" attack with a Mom's Heart-esque BulletHell attack. And, of course, he still has a [[DamageSpongeBoss ridiculously large health pool]]. To top it off, Greed Mode can make you fight Mega Fatty on the ''first floor''. Annoying enough if it's the regular version, but if it's a champion, you might as well restart.
* The Stain, the upgraded form of Polycephalus. Like the original, it spends most of its time underground, popping up only to attack. While this is predictable most of the time, if you don't get it to pop up before it disappears, then you have no idea where on the field it will show up. This means it can easily get in your face to use its CombatTentacles attack, which is very fast and has virtually no tell aside from the Stain appearing in front of you. That is, if it doesn't go for just popping up ''[[TeleFrag directly underneath you]]'' for unavoidable contact damage. All of this is before we talk about its [[ThatOneAttack strongest attack]]: if it pops up as a single face, it unleashes a BulletHell attack with a volume comparable to ''Mom's Heart''. Finally, Greed Mode can pit you against ''two Stains at once'', or, if you're really unlucky, '''three'''. Watch out if they all use their BulletHell attack ''[[OhCrap at the same time]]''. To make matters ''even worse'', it can show up as early as ''the Caves''.

* If you thought the TrueFinalBoss fight against Mega Satan in ''Rebirth'' was brutal, you're far from the worst. Enter '''[[EldritchAbomination Hush]]'''. Reach Mom's Heart or It Lives and beat them in under 30 minutes to get access to its lair, a place called ???. Before the fight, the room gives you two item rooms (with two item options to choose from on each room), four golden chests, and a shop. Needless to say, ''you will need them''. You'll first face Hush as a glorified ???, but defeating it is not the end of it, as it reveals [[OneWingedAngel its true form]]. With [[SequentialBoss five phases to the true form's battle]], loads and loads of BulletHell attacks that make bosses from ''Franchise/TouhouProject'' blush (and some of which wrap around the room's boundaries), the ability to [[FlunkyBoss spawn loads and loads of enemies]] to block your shots unless you have a piercing attack, the ability to merge with the floor to completely avoid your attacks, and the [[DamageSpongeBoss second-highest HP pool]] at [[NumberOfTheBeast 6666 HP]] on top of damage resistance that scales with your current damage, you're in for [[MarathonBoss the actual longest fight in the game]], no matter your item build. It's easy to get hit by its attacks as it is, so you also better hope you came in to its battle packing a lot of health... unless you're playing as [[OneHitPointWonder The Lost]] or [[ScrappyMechanic The Keeper]], in which case... [[ThisIsGonnaSuck good luck]], '''[[NintendoHard you'll need it]]'''.

* [[TookALevelInBadass Rag Mega!]] [[SarcasmMode Because Rag Man wasn't enough!]] He bounces around the room like Husk, but can periodically become invincible by wrapping himself in bandages, similar to a Host. He also has three purple orbitals surrounding him that can't be destroyed, making it even harder to hit him. As he loses a certain amount of health, he will start dispersing his orbitals, one by one, which will then follow the player (while actually making him easier to hit); if your speed is low, they will constantly harass you. On top of that, like Rag Man, Rag Mega can spawn Raglings to assist him, but thankfully, instead of reviving them on the spot, he summons several pillars of purple light that, while they can damage you, aren't guaranteed to home in on and revive any dead Ragling they come in contact with. All of this makes Rag Mega as dangerous as his inferior form, despite having pitiful health[[note]]120 HP[[/note]] compared to him. ''Repentance'' buffed bombs to make them deal 100 HP, which means that if you've got some to spare, you ''should'' go for it as after a few shots, you'll simply defeat him in one go.
* [[ScrappyMechanic Damage resistance]] is generally accepted because the only bosses that have it in ''Afterbirth'' are "superbosses". ''Afterbirth+'' breaks this rule with Big Horn, a Catacombs DamageSpongeBoss who will usually take the same amount of time to kill no matter where you fight him. The only way to deal decent damage is via FeedItABomb, but it's hard to pull off. His other tricks include tossing many varieties of bombs (all of which deal a full heart of damage), trying to corner you with slapping hands, and [[MookMaker summoning a weakened]] [[DegradedBoss Little Horn]]. An update quickly reduced his health [[note]]from 600 HP to 480 HP[[/note]] and gave his attacks a little more delay, whereas one released a month later (most importantly) removed his damage resistance; nevertheless, he's still a pain to fight.
* The Sisters Vis, an alternate form of The Cage. Where to begin? DualBoss? Check. [[DamageSpongeBoss High health]] (between both sisters[[note]]350 HP per sister, for a total of 700 between both[[/note]])? Check. [[FlunkyBoss Summons smaller Vis enemies]]? Check. Rolls around the arena (with the added bonus of one of them occasionally [[TurnsRed Turning Red]] and moving faster than usual)? Check. Surviving sister TurnsRed if you kill one of them? Check. [[WaveMotionGun Gigantic Brimstone laser]] that can wave back and forth with an enormous amount of coverage if only one of them fires it? ''[[ThatOneAttack Dear God check]].'' Their health even used to be higher, before updates considerably nerfed it [[note]]first from 800 HP to 500 HP per sister, then to 350 HP per sister[[/note]]. As an added bonus, in Greedier mode, you may find yourself fighting ''eight of them at once''! Good luck, you're gonna need it!

* Thought that bosses like The Bloat, The Adversary, The Cage, or Sisters Vis were painful? The Forgotten update adds The Matriarch, an unholy mix between Fistula, Chub, and the Chubber and Fistuloid enemies that's [[DamageSpongeBoss even sturdier]][[note]]at 700 HP[[/note]], and who can appear on ''any'' environment of the Womb (but as of ''Repentance'', appears most commonly in the Scarred Womb). The Matriarch shoots Chargers in the eight cardinal directions, spawns Fistuloids that surround her, and shoots a jumbo tear that leaves a puddle of toxic blood creep. As she takes damage, she sheds small Fistulas and Fistuloids which shoot Chargers like Chubber does. At medium health, she starts summoning [[ZergRush an enormous wave of Fistuloids that immediatly shoot their Chargers at you]]. When "killed", the Chub sheds her Fistula armor completely, spawning even more Chargers, Fistulas and Fistuloids. Lastly, unlike the normal version of Chub, this one [[DefiedTrope defies]] the FeedItABomb strategy by [[HoistByHisOwnPetard spitting it back at]] [[NoYou you]]; only The Forgotten can avoid this attack by [[TennisBoss swinging the bomb back at her]] with his bone. It's virtually impossible to avoid getting hit simply because the Matriarch is big enough, her spawns are numerous enough, and her attacks are quick enough, that there is just nowhere in the room you can hide. As a result, to many, this boss became the new Bloat for the final days of ''Afterbirth+'', being considered ''even'' harder than the non-tankiest final bosses in the game, and unlike bosses like Sisters Vis and Big Horn, was never nerfed - it took until ''Repentance'' where this hellspawn was '''''finally''''' {{nerf}}ed, causing her to [[CastFromHitPoints take 30 HP of damage when she summons a Fistuloid]], making the Fistuloids that orbit her attack less aggressively, and shedding less pieces of Fistula armor when she's weak - nevertheless, she's remains a very dangerous boss.
* '''Delirium'''. In addition to having an absolutely titanic amount of HP,[[note]]10,000, the highest HP of any enemy tied with The Beast[[/note]] its attacks are hard to dodge as they are, with very convoluted and tight patterns of bullets fired with barely any downtime, some of which can be ipecac shots. No matter what Delirium transforms into, though, expect to be annoyed by his propensity to teleport around the room at random (often [[TeleFrag right besides you]]) and the fact that he gets faster as his health gets lower. Even so, the amount and type of bosses that you encounter, combined with the [[GameBreaker build you amassed before the fight]], are what will make Delirium either a boss whose forms are [[CurbStompBattle only a nuisance while dealing with its bullet patterns]], or a [[NintendoHard true nightmare of a boss that]] [[MarathonBoss you'll have to outlast]]. It doesn't help that the level you find Delirium in, [[MarathonLevel The Void]], has [[GoddamnedBats enemies]] [[DemonicSpiders of all types]] that will cause you to hope you can hold onto your life, as well as bosses that Delirium can transform into during the fight... yes, that includes all and each of the other bosses on this page (up to ''Afterbirth+'') [[note]]except for Hush, unless you encounter ''very'' few bosses throughout your run[[/note]]. It gets to the point where most consider it even harder than '''THE BEAST''', ''Repentance'''s TrueFinalBoss.

* [[DemBones The Pile]], who curiously is an even "[[BuffySpeak undeader]]" version of Polycephalus and the "[[BackFromTheDead undead]]" version of Stain, but [[CameBackStrong manages to be even more dangerous and aggressive than the two]]. It can summon lines of spikes to sting you, burrow underground at high speeds to quickly emerge and pelt you with bone shots three times, and charge at you at pretty much the same speed that Dangle and Gurdy Jr. would, but making bones rain behind itself similarly to Bumbino. It can also summon [[GoddamnedBats Bonies]], which will prove to be just the right distraction in the battle. On top of all this? The Pile has a pretty respectable HP pool[[note]]580 HP[[/note]], not huge but just high enough to make it just as dangerous as bosses like The Cage in combination with its attacks. It mainly appears in chapter 3's Necropolis, but it can also appear in the Ashpit in the alternate path.

* The Scourge is the KingMook to [[DemonicSpiders the Whipper and Cultist families]]. Sounds painful enough? '''''Because it is!''''' While its green multi-projectile attack is a fairer one to dodge (even if it spawns [[TheGoomba Small Maggots]]), it also makes a lot of use of its tendrils to [[WhipItGood lash at you]] and the walls. It has three variations to this attack: lashing one at you and dragging it at the wall to fire projectiles and maggots, firing one at you and another at the wall then rotate them while firing rings of projectiles, or embedding both at the wall while indulging in BulletHell. And no, you can't leave the area you are in if it corners you; the tendrils are solid, so you ''will'' have to survive the projectile onslaughts. And lastly, it hovers to the center of the room while sucking you and streams of shots in, often changing the directions of the streams, meaning that you'll have to backtrack in order to not get cornered. To boot? The Scourge has [[DamageSpongeBoss a collossal amount of HP]][[note]]950 HP, which is that of Mon's Heart/It Lives[[/note]], so you will stay a very long while either [[MarathonBoss trying to outlast this hellspawn]], or [[HaveANiceDeath die trying]].
* [[TookALevelInBadass Mother, the renamed Witness]], is far more of a threat than in ''Antibirth''. For one thing, you don't have a lot of room to work with compared to Antibirth making dodging her attacks far more difficult. She also doesn't have a health bar and has a crapload of health to boot. And the attacks themselves include summoning a crapload of gapers that take up a lot of space in the already small room walking up to her and her hitting towards you. The worst one though has to be when she pukes out a Fistula and smacks it around with bullets (and if you live then the pieces of it.) going everywhere. And that's just phase 1. Phase 2 begins after shooting a laser out of nowhere and then coming out to fight you the same way she did in Antibirth. She doesn't move around much but she's also blocking off a good part of the room. Her attacks include jumping up and charging before crashing down in the center sending shockwaves and her sucking bullets up to them spit out at you. Have fun with the Tainted characters, especially The Lost and Jacob!

* The Cage, which is pretty much an oversized Vis. For starters, he's the posthumous version of Mega Fatty, an already [[DamageSpongeBoss spongy boss]], and [[UpToEleven as a result has the highest health of any standard boss in the game at 800 HP]], higher than that of any boss including ''[[DiscOneFinalBoss Mom]]'' (with the exceptions of the other final bosses). As for his choices of combat, he possesses a rolling attack that is similar to Gurdy Jr's charge but without the ability to slow the boss with knockback; only slowing tears can impede it. The real show-stopper, however, is his jump attack that sends out waves of stone that curve completely randomly and are impossible to predict. And yes, there's the chance of seeing two of them in one room in the final levels. ''Afterbirth'' introduces a pink champion version of two Cages, which can result in a Double Trouble room having ''four Cages at once''.

* '''[[TrueFinalBoss Delirium]]'''. In addition to having an absolutely titanic amount of HP,[[note]]10,000, the highest HP of any enemy tied with The Beast[[/note]] its attacks are hard to dodge as they are, with very convoluted and tight patterns of bullets fired with barely any downtime, some of which can be ipecac shots. No matter what Delirium transforms into, though, expect to be annoyed by his propensity to teleport around the room at random and the fact that he gets faster as his health gets lower. Even so, the amount and type of bosses that you encounter, combined with the [[GameBreaker build you amassed before the fight]], are what will make Delirium either a boss whose forms are [[CurbStompBattle only a nuisance while dealing with its bullet patterns]], or a [[NintendoHard true nightmare of a boss that]] [[MarathonBoss you'll have to outlast]]. It doesn't help that the level you find Delirium in, [[MarathonLevel The Void]], has [[GoddamnedBats enemies]] [[DemonicSpiders of all types]] that will cause you to hope you can hold onto your life, as well as bosses that Delirium can transform into during the fight... yes, that includes all and each of the other bosses on this page (up to ''Afterbirth+'') [[note]]except for Hush, unless you encounter ''very'' few bosses throughout your run[[/note]]. It gets to the point where most consider it even harder than '''THE BEAST''', ''Repentance'''s TrueFinalBoss.

* Colostomia. Not only winning [[NauseaFuel the most disgusting boss]] in ''Repentance'' yet she's also one of the hardest. On top of being [[DamageSpongeBoss an already tanky boss]][[note]]380 HP[[/note]] (even tankier than the Basement's Dangle), all of her attacks are dangerous. She slides around really fast, leaving explosive gas clouds which react to bomb explosions. She also fires out butt bombs that detonate these same gas clouds, on top of the explosions having [[HitboxDissonance varying range to their size]]. Unless you pay attention to the gas the charge leaves behind, you won't have a tell at all. When low on health, Colostomia will now start to spew out the bombs while jumping around and leaving brown creep that, unlike other types of the same creep, hurts you. And here's the worst part: this is only in chapter 1! Thank goodness she only appears in, fittingly enough, Dross.
* Hornfel, from the Mines. This bugger tends to use hit and run methods to kill you. And they are nearly all explosive (with one exception though that comes AFTER he pelts bombs like a maniac) so unless you have the Wafer or something that makes you immune to explosives like Host Hat, you are going to lose a ton of hearts (or runs) from him. By the way, remember his attack where he sends dummies of himself? It was ''buffed'' to include three now. All with bombs if you hit one by mistake. Prepare to rage if you are Tainted Lost!

* The Heretic is an advanced form of The Haunt, and he lives up to his predecessor's reputation and then some. He starts the fight sending five flunkies with homing bullets at you — potentially [[GoddamnedBats annoying]], but not difficult. But when they go down, The Heretic himself starts attacking, and pain ensues. He can charge at you repeatedly from alternating sides of the room for a full heart of damage, and to make things worse, he will home in on you slightly and can fake you out on the last charge. In addition, he can rain homing explosive tears at you from above, and possesses a Brimstone attack that bounces between the fireplaces in his boss room and will likely take up most of the room. It's not uncommon for players to leave the fight with five or six hearts less than they had when they entered. Thankfully, ''Repentance'' at least made his explosive tear attack easier to dodge since the tears leave target markers on the ground.
* [[TookALevelInBadass The alternate path's Mom is much more deadly than her Depths counterpart.]] Her monster summons include Psychic Horfs, [[DemonicSpiders Rag Blisters]] and Cursed Globins which are much more deadly than the Depths could ever be. If you face her in the alternate floor, [[ThatOneLevel Gehenna]], you'll also have to contend with that floor's DemonicSpiders as well. Her "safe" eye will now a fire twin Brimstone laser you are in sight. And finally, her stomp has a chance to instead be three quick stomps, with the third one [[ThatOneAttack leaving rows of explosions in four directions that can't be blocked by Host Hat or Pyromaniac]], because why not? If there was a time to use the Bible, then now would be the time.
* [[TookALevelInBadass Mother, the renamed Witness]], is far more of a threat than in ''Antibirth''. For one thing, you don't have a lot of room to work with compared to Antibirth making dodging her attacks far more difficult. She also doesn't have a health bar and has a crapload of health to boot. And the attacks themselves include summoning a crapload of gapers that take up a lot of space in the already small room walking up to her and her hitting towards you. The worst one though has to be when she pukes out a Fistula and smacks it around with bullets (and if you live then the pieces of it.) going everywhere. And that's just phase 1. Phase 2 begins after shooting a laser out of nowhere and then coming out to fight you the same way she did in Antibirth. She doesn't move around much but she's also blocking off a good part of the room. Her attacks include jumping up and charging before crashing down in the center sending shockwaves and her sucking bullets up to them spit out at you. Have fun with the Tainted characters, especially Lost and Jacob!

* [[TookALevelInBadass The alternate path's Mom is much more deadly than her Depths counterpart.]] Her monster summons include Psychic Horfs, [[DemonicSpiders Rag Blisters]] and Cursed Globins which are much more deadly than the Depths could ever be. If you face her in the alternate floor, [[ThatOneLevel Gehenna]], you'll also have to contend with that floor's DemonicSpiders as well. Her safe eye is now a laser that will fire if you are in sight. And finally, her stomp has a chance to instead be three quick stomps, with the third one [[ThatOneAttack leaving rows of explosions in four directions that can't be blocked by Host Hat or Pyromaniac]], because why not? If there was a time to use the Bible, then now would be the time.

* '''[[TrueFinalBoss Delirium]]'''. Its attacks are hard to dodge as they are, with very convoluted and tight patterns of bullets, some of which can be ipecac shots. No matter what Delirium transforms into, though, expect to be annoyed by his propensity to teleport around the room at random and the fact that he gets faster as his health gets lower. Even so, the amount and type of bosses that you encounter, combined with the [[GameBreaker build you amassed before the fight]], are what will make Delirium either a boss whose forms are [[CurbStompBattle only a nuisance while dealing with its bullet patterns]], or a [[NintendoHard true nightmare of a boss that]] [[MarathonBoss you'll have to outlast]]. It doesn't help that the level you find Delirium in, [[MarathonLevel The Void]], has [[GoddamnedBats enemies]] [[DemonicSpiders of all types]] that will cause you to hope you can hold onto your life, as well as bosses that Delirium can transform into during the fight... yes, that includes all and each of the other bosses on this page (up to ''Afterbirth+'') [[note]]except for Hush, unless you encounter ''very'' few bosses throughout your run[[/note]]... yes, it's even harder than '''THE BEAST''', ''Repentance'''s TrueFinalBoss.

* [[TookALevelInBadass Rag Mega!]] [[SarcasmMode Because Rag Man wasn't enough!]] He bounces around the room like Husk, but can periodically become invincible by wrapping himself in bandages, similar to a Host. He also has three purple orbitals surrounding him that can't be destroyed, making it even harder to hit him. As he loses a certain amount of health, he will start dispersing his orbitals, one by one, which will then follow the player (while actually making him easier to hit); if your speed is low, they will constantly harass you. On top of that, like Rag Man, Rag Mega can spawn Raglings to assist him, but thankfully, instead of reviving them on the spot, he summons several pillars of purple light that, while they can damage you, aren't guaranteed to home in on and revive any dead Ragling they come in contact with. All of this makes Rag Mega as dangerous as his inferior form, despite having pitiful health[[note]]120 HP[[/note]] compared to him.

* The Cage, which is pretty much an oversized Vis. For starters, he's the posthumous version of Mega Fatty, an already [[DamageSpongeBoss spongy boss]], and [[UpToEleven as a result has the highest health of any standard boss in the game at 800 HP]], higher than that of any boss including ''Mom'' (with the exceptions of the other final bosses). As for his choices of combat, he possesses a rolling attack that is similar to Gurdy Jr's charge but without the ability to slow the boss with knockback; only slowing tears can impede it. The real show-stopper, however, is his jump attack that sends out waves of stone that curve completely randomly and are impossible to predict. And yes, there's the chance of seeing two of them in one room in the final levels. ''Afterbirth'' introduces a pink champion version of two Cages, which can result in a Double Trouble room having ''four Cages at once''.

* Death, the final Horseman, is able to summon Scythes that home in on you. It's limited homing, but they are huge and hard to dodge. After you've damaged him enough, his mount detaches with its own health and charges endlessly, even ''after you've killed him''. On top of that, he spawns Knights.

* '''[[TrueFinalBoss Delirium]]'''. Its attacks are hard to dodge as they are, with very convoluted and tight patterns of bullets, some of which can be ipecac shots. No matter what Delirium transforms into, though, expect to be annoyed by his propensity to teleport around the room at random and the fact that he gets faster as his health gets lower. Even so, the amount and type of bosses that you encounter, combined with the [[GameBreaker build you amassed before the fight]], are what will make Delirium either a boss whose forms are [[CurbStompBattle only a nuisance while dealing with its bullet patterns]], or a [[NintendoHard true nightmare of a boss that]] [[MarathonBoss you'll have to outlast]]. It doesn't help that the level you find Delirium in, [[MarathonLevel The Void]], has [[GoddamnedBats enemies]] [[DemonicSpiders of all types]] that will cause you to hope you can hold onto your life, as well as bosses that Delirium can transform into during the fight... yes, that includes all and each of the other bosses on this page (up to ''Afterbirth+'') [[note]]except for Hush, unless you encounter ''very'' few bosses throughout your run[[/note]]...