With so many bosses in this game, there was bound to be a few that look threatening, but end up underwhelming in practice. Moreso if you were lucky enough to get a Game-Breaker build that tears the whole run apart.
- Mom's Heart/It Lives will rarely pose a serious threat to anyone who is good enough to reach it. It is considerably more of a challenge in Rebirth, however.
- The red champion version of Mom looks impressive, but is actually far easier to beat due to her greater attack speed and lack of Mook Maker abilities. Players can just dodge the telegraphed foot attack and retaliate, occasionally dodging a bullet spread from her eye. It can be troublesome if you have one of the Fetus items, however, as you have to time them very carefully to land a hit and thus the fight drags out for much longer.
- Satan in Rebirth. While his fellow Final Bosses received new tricks which generally made them much more impressive than they were in the original game, Satan stayed more or less the same, with only a couple of new attacks added in only one of his phases, which are quite similar to the attacks he already had. Add the increased potential for powerful item combinations, and he just Can't Catch Up.
- ???/Blue Baby. For starters, it has the exact same health pool as Isaacnote , who was encountered in the previous floor. In Wrath of the Lamb, it was essentially a carbon copy of Isaac. But it did receive a few changes in Rebirth (e.g. being able to occasionally fire homing projectiles), but even with these changes, it's still a very underwhelming boss. First off, it doesn't seem to fire out as many projectiles as Isaac. It doesn't even have the attack that covers the whole room with Crack the Sky light beams. What it does have, however, is the ability to summon Attack Flies and Pooters, which should be incredibly easy to destroy at this point in the run. Even with the two Eternal Flies orbiting Blue Baby, it's still fairly easy to deal damage to it. In Afterbirth, its status as an underwhelming boss was made worse when Hush came along. Hush's first form uses the same attacks as ???/Blue Baby, but then manages to have a final form. It also has an incredibly strong damage-reduction armor that reduces the amount of damage it takes after consecutive hits. But ???/Blue Baby, however, did not receive any changes whatsoever going into Afterbirth. It had the exact same Can't Catch Up problem that Satan had during its transition into Rebirth. The worst part, however, is that Blue Baby is a Chapter 6 boss, which should be harder than the boss in Chapter 5, not easier.
- Ultra Greed in Afterbirth is undeniably a fun battle, and it does take a while to win thanks to his scaled health gimmick. That said, given how easy it is to collect powerful items over the course of the run, coupled with the fact that Ultra Greed's attacks are telegraphed well in advance, he'll only pose a real challenge to characters with low health (i.e. the Lost) or those with low speed attacks. A patch buffed the health of his giant coins, making them more likely to survive the player's attacks, which means he gets to summon more mooks and recover more health (not to mention the bombs, though those are the easiest to dodge). He also Turns Red as his health drops, making the fight much more challenging. Greedier Mode in Afterbirth Plus fixes this further by giving Ultra Greed a second phase, in which he throws explosive coins all over the place while leaping to cause rock shockwaves and firing brimstone lasers out of the golden doors. A much faster-paced and hectic battle... that comes with its own weakness — as most of Ultra Greedier's attacks are explosive-based, the Pyromaniac and Host Hat items rocket him back into Anticlimax.
- Delirium zig-zags on this. Against most characters, Delirium is pretty easy to beat as long as you have good damage and a fair amount of spare health (very likely, especially since you can get a bunch of new items from the many boss battles in the Void). With certain combos, it can be killed faster than Mega Satan. What's more, its base form has absolutely no damage-reduction armor whatsoevernote , allowing it to be obliterated most easily in this state. But against the Glass Cannon characters like Keeper and the Lost, its constant teleporting (frequently into you for unavoidable damage) and Bullet Hell can make the fight almost a Luck-Based Mission.
- The True Final Boss of Repentance. The Beast is considered one of the easiest parts of the Home Boss Bonanza, despite being the last of them. Most of it is a pretty straight forward chase sequence at the beginning and end where the most trouble comes from dodging the stalagmites and stalactites, and outside of that its attacks are easy to figure out and remember. The Beast is this to a lesser degree than most other bosses because of how she is fought immediately after a series of five bosses, with Dogma, Ultra War, and Ultra Death especially infamous for their difficulty. Reaching the Beast herself is not that easy, but once you do, the run is usually won from there.
- In general, pretty much any boss becomes this once you've gotten a good enough build to completely demolish them almost right as the battle starts. Even if it's not a one-shot, you can still seriously shred their health with little effort. The only exceptions are the bosses with "armor"note due to how they have damage reduction scaling and multiple phases. Although with a truly insane build, even they can be destroyed in seconds.
