At the end of each floor, the player must fight a boss. The boss will be randomly chosen based on which area the player is currently in. Some bosses can be specially coloured like normal enemies, which can change their pattern somewhat; this occurs more often once the player has beat the full game for the sixth time and onwards.
Upon death, bosses either drop an item which increases a single stat or an item unique to that particular boss. In addition, they drop random health pickups; two at the start or one after unlocking "Everything is Terrible". If the boss was an alternative version, it drops one additional random health pickup upon death.
Datei:Mask of Infamy ..png Datei:VS DaddyLonglegs.png Datei:200x300-400px-Triachnid boss portrait.png Datei:Carrionqueen.png Datei:The Wretched.png Datei:Bc Bloat.png Datei:Loki full.png Datei:BC War.png Datei:250x250-400px-Mom.png
Scolex_full.png|Scolex|link=Scolex Blastocyst full.png|Blastocyst|link=Blastocyst Bc_Bloat.png|The Bloat (Wrath of the Lamb)|link=The Bloat VS DaddyLonglegs.png|Daddy Long Legs (Wrath of the Lamb)|link=Daddy Long Legs 200x300-400px-Triachnid boss portrait.png|Triachnid (Daddy Long Legs' Alt) (Wrath of the Lamb)|link=Triachnid VSDeath.png|Death (Horseman of the Apocalypse)|link=Death BC Conquest.png|Conquest (Death's Alt)|link=Conquest Moms Heart Full.png|Mom's Heart (Final boss of The Womb)|link=Mom's Heart 250x250-ITLIVEScutout.png|It Lives (Mom's Heart Alt)|link=It Lives </gallery>
(Wrath of the Lamb expansion)
Added in the Halloween update, 100% chance to enter after ending 10. Defeating Mom's Heart without taking a hit prior to the 10th ending increases your chances to enter.
Added in Wrath of the Lamb, 100% chance to enter after ending 10.
(Wrath of the Lamb expansion v1.3)
After defeating Isaac while holding The Polaroid trinket, opening the golden chest in the middle will take you to The Chest instead of displaying ending 12.
(Except for floors where "final bosses" appear.)
Unlockable BossesBearbeitenmeat cube upon defeat, and the player can fight all of them in one playthrough by using the Book Of Revelations.
- Famine (The Basement)
- Pestilence (The Caves)
- War (The Depths)
- Death (The Womb)
- Headless Horseman (May appear as a boss in almost any floor.)
- Conquest (Added in the Wrath of the Lamb expansion.)
These bosses are only available after finding their respective unlocks.
- Steven (Alt for Gemini, unlocked by completing The Basement 25 times)
- C.H.A.D. (Alt for Chub, unlocked by completing The Caves 20 times)
- Gish (Alt for Monstro II, unlocked by completing The Depths 15 times)
- Triachnid (Alt for Daddy Long Legs unlocked by completing The Womb 15 times)
- It Lives (Replaces Mom's Heart, unlocked after beating Mom's Heart nine times)
Each level has a chance to include a Special Room where the player can face a mini-bossWrath of the Lamb expansion and will sometimes appear instead of the regular version of the accordant Deadly Sin.
|Wrath of the Lamb additions|
|Boss Specific Drops|
- If you have extra lives, either from collecting a 1UP, Ankh, or Guppy, bosses can be re-fought at the cost of one life in order to collect more items. After defeating a boss, don't immediately pick up the item on the pedestal. Instead, kill yourself with bombs or spikes, fires, etc. You will respawn outside the boss room, and the boss will return to life. You can fight the boss a second time to produce a second item. This can be done as many times as you have extra lives.
- Most of the bosses, in particular ones like Gemini, are heavily suggested to be the lost siblings of Isaac. How most of Isaac's "siblings" survived in the murky depths of the basement is unknown, although it is clear that many of them have adapted, and in cases like Peep, have developed grotesque abilities to use to defend themselves. Considering that many of them are very deformed, it's possible that the bosses are failed (or successful) abortions of Isaac's mother's other pregnancies.
- Other bosses seem to be mutated animals/insects, such as Chub and Larry Jr. How they became this way is unknown.
- The Health Bar at the top of the screen for each boss (excluding Mask of Infamy) has an angry face to the left of it. This is a reference to the Newgrounds site, where a character called Mr. Angry Face is known for that symbol.