History ThatOneBoss / TheBindingOfIsaac

* In general, any boss that spawns in a closet room[[note]](1 x 0.5 the size of a normal one)[[/note]]. Anyone with [[ThatOneAttack Brimstone attacks]] can be nearly impossible to dodge. Even {{Breather Boss}}es like Pin and Famine can be much harder with such a tiny space to maneuver around them. And lord have mercy if you happen to fight one of the bosses from this page...

* [[TrueFinalBoss Delirium]] {{zig|ZaggingTrope}}-zags on this and AntiClimaxBoss. Its attacks are hard to dodge as they are, with very convoluted and tight patterns of bullets, some of which can be Ipecac shots. Even so, the amount and type of bosses that you encounter, combined with the build you ammased before the fight, are what will make Delirium either a boss whose forms are only a nuisance while dealing with its bullet patterns, or a true nightmare of a boss that 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 in to your life, as well as bosses that he can transform on during the fight... yes, that includes all and each of the other bosses in this page...

* The Blighted Ovum, Gemini's 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 it has half the health of 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.

* Carrion Queen 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 almost impossible to see, but will also cause major damage to the other bosses, potentially killing them ''in a few seconds''.

* 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'' 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 advanced version of the Dark One. The one and only thing that stands out about the Adversary is that he fires a Brimstone laser that ''homes in on 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, you're ''toast''.

* [[TookALevelInBadass Rag Mega!]] [[SarcasmMode Because Rag Man wasn't enough!]] Introduced in ''Afterbirth+'', 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 he will not revive them like Rag Man does, instead summoning several pillars of purple light that can damage you on top of reviving any dead Ragling they come in contact with. All of this makes Rag Mega a much bigger step up from his inferior form, despite having pitiful health[[note]]120 HP[[/note]] compared to him.
* [[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[[note]]with 480 HP[[/note]] 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]]. Updates quickly gave his attacks more delay and (most importantly) removed his damage resistance, but he's still a big pain to fight.

* ''Afterbirth+'' 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.]]
* The Forgotten update adds The Matriarch, an unholy mix between the Chubber enemy, Fistula, and Chub. As the Matriarch takes damage, she sheds small Fistulas and Fistuloids which shoot Chargers like Chubber does. The Matriach herself also shoots Chargers in the eight cardinal directions. When killed, she spawns a Chub and more Fistulas and Fistuloids. Lastly, unlike the normal version of Chub, this one defies the FeedItABomb strategy by spitting it back at you; only The Forgotten can avoid this attack by swinging the bomb back with his bone. It's practically impossible to avoid getting hitting simply because the boss is big enough, and her spawns numerous enough, that there is almost nowhere in the room you can hide.

* The Fallen can be difficult if encountered early in the game or when damage output is low. It attacks primarily with fast spreads 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 independenly, resulting in bullet and brimstone hell and can quickly ruin your run if you don't take at least one of them out quickly.

* Carrion Queen 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. The champion version is actually better, because she instead poops out tiny heart enemies which are easy to kill. 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 almost impossible to see, but will also cause major damage to the other bosses, potentially killing them ''in a few seconds''.

* The Cage, which is pretty much an oversized Vis. For starters, [[DamageSpongeBoss he has the highest health of any 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 possess a rolling attack that is similar to Gurdy Jr's charge but without the ability to slow the boss with knockback; only slowing tears. 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''.

* In general, any boss that spawns in a closet room[[note]](1 x 0.5 the size of a normal one[[/note]]). Anyone with [[ThatOneAttack Brimstone attacks]] can be nearly impossible to dodge. Even {{Breather Boss}}es like Pin and Famine can be much harder with such a tiny space to maneuver around them. And lord have mercy if you happen to fight one of the bosses from this page...

* Monstro II is a huge step up from his first form. His attacks are much harder to dodge, as instead of his original's short-range blood bullet wave attack, he fires brimstone lasers and circles of bullets that pierce across the boss arena, and spawns flies that also fire bullets at you. He's also much more [[DamageSpongeBoss damage-sponging]], being at a whopping 633 base HP (which is slightly more than Mega Fatty's) instead of his original's 250.

* The Blighted Ovum, Gemini's 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 it has half the health of Gemini. Still, if you can't kill Contusion quickly by then, and you lack flight, you are very screwed.

* '''The Bloat'''. Providing the page's picture, this guy has very good reasons to why [[TheScrappy he is hated so much]] by the community. As the posthumous version of Peep, it has slightly more health that him, and shares most of its same strategy. However, the eyes detach at start, not after taking enough damage like Peep does. Its most ruthless attack is that he invariably fires Brimstone if you so much as graze the area directly to the sides or in front of him; this attack is not telegraphed, either. Unless you've got high speed, this will hit you. 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. If you get to [[spoiler:The Chest (or the Dark Room in ''Rebirth'')]], always have more than one heart in case he turns up unannounced.
** Afterbirth+ has a challenge called "April Fool's", 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. Fortunately, it also introduced the very useful Analog Stick item, allowing you to shoot diagonally, making the battle against the Bloat much more simple.

* 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 [[SarcasmMode best part]]? He's a ''Cellar'' 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 Cage, which is pretty much an oversized Vis. For starters, [[DamageSpongeBoss he has the highest health of any boss in the game]] (with the exceptions of the final bosses), higher than that of Gurdy and even ''Mom''. As for his choices of combat, he possess a rolling attack that is similar to Gurdy Jr's charge but without the ability to slow the boss with knockback. 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''.

* Rag Man, especially when encountered as your first boss. Not only is he a FlunkyBoss, his summons are tanky as hell (they have ''more'' health than the usual Ragling enemies) and fire homing shots. If he's not killed quickly, he can summon up to three of them, and will keep respawning them throughout the fight. However, Rag Man is one of the smaller bosses in the game and tends to walk away from the player, making him hard to actually hit. Then you throw in his HealThyself ability on top of all that. If you have low damage, be prepared to take some hits.

* In general, any boss that spawns in a closet (1x0.5 size) room. Anyone with Brimstone attacks can be nearly impossible to dodge. Even {{Breather Boss}}es like Pin and Famine can be much harder with such a tiny space to maneuver around them. And Lord have mercy if you happen to fight one of the bosses from this page...

* [[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 boss 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 [[DegradedBoss summoning a weak Little Horn]]. Updates quickly reduced his health, gave his attacks more delay, and (most importantly) removed his damage resistance, but he's still a pain to fight.
* The Sisters Vis, an alternate form of The Cage. Where to begin? DualBoss? Check. [[DamageSpongeBoss Tons of health]]? 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. Gigantic Brimstone laser that waves back and forth with an enormous amount of coverage? Dear God check. To many, this boss is the new Bloat. As an added bonus, in Greedier mode you may find yourself fighting ''eight of them at once''! [[SarcasmMode Have fun!]] While they've been nerfed considerably in recent patches, they can still be a challenge. Especially if you fight them in the Depths.

* The Forgotten update adds The Matriarch, an unholy mix between the Chubber enemy, Fistula, and Chub. As the Matriarch takes damage, she sheds small Fistulas and Fistuloids which shoot Chargers like Chubber does. The Matriach herself also shoots Chargers in the eight cardinal directions. When killed, she spawns a Chub and more Fistulas and Fistuloids. It's practically impossible to avoid getting hitting simply because the boss is big enough, and her spawns numerous enough, that there is almost nowhere in the room you can hide.

* Monstro II is a huge step up from his first form. His attacks are much harder to dodge, as instead of his short-range blood bullet wave attack, he fires brimstone lasers and circles of bullets that pierce across the boss arena, and spawns flies that also fire bullets at you. He's also much more [[DamageSpongeBoss damage-sponging]], being at a whopping 633 base HP (which is slightly more than Mega Fatty's) instead of his original's 250.

* Monstro II is a huge step up from his first form. His attacks are much harder to dodge, as instead of his short-range blood bullet wave attack, he fires brimstone lasers and circles of bullets that pierce across the boss arena, and spawns flies that also fire bullets at you. He's also much damage-sponging, being at a whopping 633 base HP (which is slightly more than Mega Fatty's) instead of his original's 250.

* The Sisters Vis, an alternate form of The Cage. Where to begin? DualBoss? Check. [[DamageSpongeBoss Tons of health]]? 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. Gigantic Brimstone laser that waves back and forth with an enormous amount of coverage? Dear God check. Too many, this boss is the new Bloat. As an added bonus, in Greedier mode you may find yourself fighting ''eight of them at once''! [[SarcasmMode Have fun!]] While they've been nerfed considerably in recent patches, they can still be a challenge. Especially if you fight them in the Depths.

* The Forgotten update adds the Matriarch, an unholy mix between the Chubber enemy, Fistula, and Chub. As the Matriach takes damage, she sheds small Fistulas and Fistuloids which shoot Chargers like Chubber does. The Matriach herself also shoots Chargers in the eight cardinal directions. When killed, she spawns a Chub and more Fistulas and Fistuloids. It's practically impossible to avoid getting hitting simply because the boss is big enough, and her spawns numerous enough, that there is almost nowhere in the room you can hide.

* Gemini, one of the earliest bosses you can fight in any run, might seem like a fairly easy boss to hit because of the larger twin (Contusion)'s size, but he can easily run as fast if not faster than you, and will make light work of you if your speed is low. Once Contusion is down, his twin brother Suture will take action. Not only can he fly over obstacles, but he can cut corners and catch you out in the mess of obstacles that normally spawn in the room as well.
* Gurdy, a DamageSpongeBoss early on, can't move but takes up half the room. She can fire five bullets in a spread pattern and summons sacs that fire more bullets, as well as flies. Compared to the other bosses, she's a real pain. It's easy enough if you get her pattern down, but the fight takes a long time. You also better hope you've upgraded your damage or tears, because the bullet sacs regenerate a lot faster than spider sacs do. A lot easier if you learn to exploit the space behind her where flies spawn, even easier if she spawns an explosive Boil, which tends to hurt her more than you.

* Super Wrath. He fires homing troll bombs that pass through walls, and is tougher to kill. If you can't fly, it sucks to be you. ''Rebirth'' mercifully toned this down by making his troll bombs solid, and boss fights with him usually have indestructible blocks to stop the bombs.

* Gurdy Jr. doesn't look tough, right? Then she charges at you with ridiculous accuracy. And if she misses, she might just do a little homing slide into you. The variations and double boss versions only make her that much harder to defeat. Plus, like "her mother" Gurdy, Gurdy Jr. is one tanky boss. ''Rebirth''[='=]s Double Trouble mechanic can actually saddle you with ''four of these gals at once''.
* The Widow, a first-floor boss that jumps around like crazy, spits demonic spiders (the tiny kind), AND spawns sacs that in turn spawn more demonic spiders. Then there's a variation of this which spawns even MORE spiders, double spiders, and hopper spiders. She was thankfully toned down after release, but she's still a lot tougher than most bosses on that floor.
* The Blighted Ovum. Similar to Gemini, this one has the added "benefit" of being the same speed as the player sans-powerups and leaving behind lethal blood trails that deal '''a full heart of health in damage''', along with a "little brother" that uses Brimstone. And the blood trails stick around for ''just'' enough time that you ''will'' step on one after completing a circle around the room. If the Ovum isn't dead or close by then, and you lack flight, you are very screwed.
* The Mask of Infamy, a [[GiantMook giant copy of the mask-heart enemies]]. Don't let that description fool you. Its AI is a lot better than the mooks it takes from, 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.
* The Bloat. A ruthless version of Peep that invariably fires Brimstone if you so much as graze the area directly to the sides or in front of him. Unless you've got very high speed, this will hit you. 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. Oh, and the eyes detach at start, not after taking enough damage like Peep does. A champion version will also send out a spray of Ipecac bombs towards you whenever he jumps, and can spawn Chargers. It is also possible to fight him in both Necropolis and Utero on the same run. If you get to [[spoiler:The Chest (or the Dark Room in ''Rebirth'')]], always have more than one heart in case he turns up unannounced.
* Carrion Queen can be 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. The champion version is actually better, because she instead poops out tiny heart enemies which are easy to kill. 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 almost impossible to see, but will also cause major damage to the other bosses, potentially killing them ''in a few seconds''.

* The Forgotten Update adds the Matriarch, an unholy mix between the Chubber enemy, Fistula, and Chub. As the Matriach takes damage, she sheds small Fistulas and Fistuloids which shoot Chargers like Chubber does. The Matriach herself also shoots Chargers in the eight cardinal directions. When killed, she spawns a Chub and more Fistulas and Fistuloids. It's practically impossible to avoid getting hitting simply because the boss is big enough, and her spawns numerous enough, that there is almost nowhere in the room you can hide.

* Super Wrath. He fires the homing troll bombs that pass through walls, and is tougher to kill. If you can't fly, it sucks to be you. ''Rebirth'' mercifully toned this down by making his troll bombs solid, and boss fights with him usually have indestrcto-blocks to stop the bombs.

* Gurdy Jr. doesn't look tough, right? Then she charges at you with ridiculous accuracy. And if she misses, she might just do a little homing slide into you. The variations and double boss versions only make her that much harder to defeat. Plus, like "her mother" Gurdy, Gurdy Jr. is one tanky boss. ''Rebirth''[='=]s Double Trouble mechanic can actually saddle you with ''four of these guys at once''.

!!''Afterbirth +''

* ''Afterbirth +'' 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.]]

* The Sisters Vis, an alternate form of The Cage. Where to begin? DualBoss? Check. [[DamageSpongeBoss Tons of health]]? 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. Gigantic Brimstone laser that waves back and forth with an enormous amount of coverage? Dear God check. To many, this boss is the new Bloat. As an added bonus, in Greedier mode you may find yourself fighting ''eight of them at once''! [[SarcasmMode Have fun!]] While they've been nerfed considerably in recent patches, they can still be a challenge. Especially if you fight them in the Depths.

Throughout its long life, ''VideoGame/TheBindingOfIsaac'' has kept one thing consistent: [[ThatOneBoss really difficult bosses]]. The games are a clear case of EasyLevelsHardBosses, and when the levels are hard enough as it is, you know you're in for a treat. With so many bosses in this game series, there are some that are [[BreatherBoss/TheBindingOfIsaac definitely not this trope]], while others are just plain [GoddamnedBoss/TheBindingOfIsaac annoying or tedious to fight]].

Throughout its long life, ''VideoGame/TheBindingOfIsaac'' has kept one thing consistent: [[ThatOneBoss really difficult bosses]]. The games are a clear case of EasyLevelsHardBosses, and when the levels are hard enough as it is, you know you're in for a treat.

* 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 [[SarcasmMode best part]]? He's a ''Cellar'' 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.

!!''Afterbirth+''

* [[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 boss 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 [[DegradedBoss summoning a weak Little Horn]]. Updates quickly reduced his health and gave his attacks more delay, but he's still a pain to fight.

* The Bloat. A ruthless version of Peep that invariably fires Brimstone ''[[TheComputerIsACheatingBastard the same second you enter the room]]'', and also if you so much as graze the area directly to the sides or in front of him. Unless you've got very high speed, this will hit you. The only safe place you can attack from is behind him, and his eyes always seem to be behind him. Oh, and the eyes detach at start, not after taking enough damage like Peep does. A champion version will also send out a spray of Ipecac bombs towards you whenever he jumps, and can spawn Chargers. It is also possible to fight him in both Necropolis and Utero on the same run. If you get to [[spoiler:The Chest (or the Dark Room in ''Rebirth'')]], always have more than one heart in case he turns up unannounced.

* 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 do-not-touch spots. Once you get to his second stage it is easy... good luck getting to his second stage one more than a heart or two. He's even worse in ''Rebirth'', as his ipecac blasts are faster.

* The Sisters Vis, an alternate form of The Cage. Where to begin? DualBoss? Check. [[DamageSpongeBoss Tons of health]]? 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. Gigantic Brimstone laser that waves back and forth with an enormous amount of coverage? Dear God check. To many, this boss is the new Bloat. As an added bonus, in Greedier mode you may find yourself fighting ''eight of them at once''! [[SarcasmMode Have fun!]]

* ''Afterbirth +'' 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.

* 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 shots, 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 of 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.