| The Lost |
The Lost starts with no health and cannot increase it by any means. Therefore, it will die from any hit. The Lost starts with flight, Spectral tears, the D4 (if unlocked) and Holy Mantle (if unlocked and after donating 879 coins to the Greed Machine). The Lost can take devil deals for free and activate the button in Greed Mode without taking damage.
- Many of the game's items provide no benefit to The Lost; for example, those that affect health or trigger on taking damage.
- Resurrection items like Dead Cat will still work with The Lost, but the life number does not appear on the HUD.
- Devil deals, while free, still count as making a deal with the devil and will prevent angel rooms from opening. Thus, a Credit Card is still recommended, or getting Chaos to acquire angel room items (except broken key pieces).
- D100 - Complete the Boss Rush.
- -0- Baby - Defeat Mom's Heart or It Lives on Hard.
- The Mind - Defeat Satan.
- Isaac's Heart - Defeat Isaac.
- The Soul - Defeat The Lamb.
- The Body - Defeat ???.
- Zodiac - Defeat Ultra Greed.
- Dad's Lost Coin - Defeat Ultra Greedier.
- Sworn Protector - Defeat Hush.
- White Baby - Defeat Mega Satan.
- Holy Card - Defeat Delirium.
- Godhead - Earn all Hard mode Completion Marks (in Rebirth, only non-DLC marks have to be completed).
Unlocking The Lost in Afterbirth
- Looking for Mom's Box in shops makes finding the poster easier.
Unlocking The Lost in Rebirth
The Lost is unlocked by dying consecutively with certain characters, with no other deaths. Deaths must be completed in the order shown here, and seeds can be used for the runs except for the last with Azazel:
- Isaac must die to a Mulliboom in The Basement or The Cellar.
- Magdalene must die to her own bomb in The Caves or The Catacombs.
- Judas must die to any Mom attack in The Depths or Necropolis. Being killed by any monster spawned by Mom will spoil the entire attempt at unlocking The Lost.
- Azazel must die to any Satan attack in Sheol. Being killed by The Fallen in the boss room or a Kamikaze Leech will spoil the entire attempt at unlocking The Lost. Being killed by using The Bible doesn't count as a Satan kill.
The Lost will be unlocked after dying to Satan's attack.
Notes on unlocking The Lost
- Multiple lives (for example, obtained by Dead Cat) must be depleted before the intended death, as deaths while having extra lives do not count as a game loss.
- Having any mods installed that triggers the mod flag will make The Lost unobtainable. In order to fix this problem, all mods have to be removed.
- The game cannot be won as any character required to unlock it when unlocking it.
- Champion versions of monsters and bosses will count for the death criteria.
- Runs can always be safely reset.
- It should be noted that Mom's Foot's stomp counts as explosive damage, which makes Pyromaniac a problematic choice when trying to complete Step 3.
- Picking the wrong character while unlocking him doesn't mess up the unlocking process.
- Quitting and Restarting the game in the middle of the unlocking process doesn't mess it up.
- Picking up Lazarus' Rags, Judas' Shadow, or Ankh should be avoided. These items will revive the current character as a different one and therefore prevent the current unlock-step from being fulfilled.
By changing a file parameter, an unsuccessful try can be undone:
- Backup the file Options.ini found in the Documents\My Games\Binding of Isaac Rebirth by making a copy of it in the same folder.
- Open the original file with Notepad and change the SteamCloud parameter in it to 0. This will disable Steam Cloud gamesaves synchronization.
- After an unsuccessful try, delete the original file and rename the backup copy with the name of the original file: Options.ini
- Repeat steps 1 after each successful run until you unlock The Lost.
- When finished, open the original file and restore the SteamCloud parameter in it to 1. This will enable SteamCloud gamesaves synchronization again.
- When The Lost's unlock requirements were discovered through the use of data mining, Edmund McMillen and Tyrone Rodriguez both expressed their disappointment, considering it impatient and "like swallowing a hundred dollar steak in one bite". 
- Right before the start of a run, there are images that appear to hint to unlocking The Lost, including the Missing Poster and The Lost itself.
- Dying in a Sacrifice Room while holding the Missing Poster would yield a puzzle piece on Isaac's last will. These puzzle pieces, when put together, created the last wills of characters dying in the method used to unlock The Lost.
- Prior to version 1.02, The Lost would die if a run was exited then continued.
- When The Lost picks up an item, tarot card, or pill, you can see its arms which do not connect to its body.
- One common (but unconfirmed) theory suggests that the single coin which The Lost starts with may be a reference to Charon's obol, a coin which was placed in the mouth of a dead person prior to burial in ancient Greek civilization. Placing the obol in the mouth ensured that the dead person would hold onto the obol after death. This obol was to be used by their ghost to pay Charon, the ferryman who would take souls across the river Styx into the underworld in exchange for a coin. Souls who did not have an obol could not pay Charon and would not be able to cross the river.
- Internally, The Lost has half a soul heart, which is hidden behind a permanent Curse of the Unknown-like effect. This causes extra lives to be hidden from The Lost's HUD. The singular soul heart is why The Lost is able to "pick up" soul hearts, black hearts, and eternal hearts. There are no ways to increase this health, though, as The Lost's health is constantly reset back to half a soul heart.
- Devil deals appear as requiring three soul hearts each as The Lost technically only has half of an invisible soul heart. This is cosmetic only, as devil deals are still free.
- In the Afterbirth DLC, a new loading screen (when Isaac dreams) depicts the "Voice of God" telling Isaac's Mom to kill her son as The Lost speaking to her from the attic.
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