To say The Binding Of Isaac is a deep game would be an understatement. What's more, is with a handful of acclaimed DLCs over the years, the game continues to get deeper. Secret levels & hidden challenges are as numerous as they are impossible to find without the aid of a guide.
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An area that is balanced quite well on this front is the playable characters. Several are quite easy to unlock, and a novice player will do it with some effort, while others are only for those who have truly mastered what the game has no offer. That's not even mentioning the tainted versions of each character, which must be unlocked separately.
Likely the first character players will unlock, Magdalene is for beginner players who need help in the rough early hours. She starts with four hearts, as opposed to the usual three, and also has a Yum Heart item to restore health. Additionally, she doesn't have any major downside, just slightly lower movement speed.
Unlocking Magdalene is pretty straightforward, but it'll take some luck. Players need to have seven heart containers at once to unlock Magdalene. There are plenty of items that give more heart containers, and they're somewhat common on early floors, so players should be able to reach this without too much trouble.
Cain does slightly more starting damage than Isaac and starts with an item that increases his luck. This comes at a price, however, and Cain only starts with two heart containers.
The method to unlock Cain is another straightforward one, but it does require a consistent amount of luck throughout a run. Players must hold 55 coins at once to unlock Cain. This is unlikely to happen naturally in a run, so player's best option is to try their hand at the slot machines if they find one and hope for good luck.
Judas starts with the "Book of Belial" item; Belial meaning wicked or worthless. Judas has notably high base damage, which is aided by the book. However, he starts with a measly one heart container.
Judas is the first character whose unlocking takes a bit of doing. Players must defeat Satan to unlock Judas. Satan can be found in the secret floor, Sheol. This floor is accessed at the end of Womb II. Sometimes after defeating Mom's Heart, but always after defeating It Lives, a Devil Door will appear containing the trapdoor that leads to Sheol.
Referred to by the fanbase as "Blue Baby", ??? is a dark character, as they are theorized to be a dead version of Isaac. ??? has slightly increased damage and speed, but their main feature is that they start with zero heart containers, instead using Soul Hearts. It goes one further than that, as it is actually impossible for ??? to ever gain heart containers. This makes ??? a character for those who want a challenge.
Unlocking ??? is simple, but will take some effort, as players must defeat Mom's Heart 10 times, meaning that players must essentially complete the game 11 times.
Eve is a surprisingly powerful character. At first glance, she may not seem it, with decreased damage and two heart containers. However, she starts with an impressive item, which boosts her damage and speed when on one red heart or less. She also starts with Dead Bird, which summons a familiar to damage enemies when she takes damage.
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To unlock Eve, players must put themselves through a challenge, as they must not pick up any hearts for two floors in a row, meaning they must be extremely careful of how much damage they take.
Samson starts the game with the Bloody Lust item, which increases his damage output whenever he takes damage. He has a slow rate of fire, but his three heart containers give players a lot of strategic possibilities.
Like Eve, Samson must be unlocked via a challenge, as players must not take any damage for two consecutive floors. It's one of the tougher challenges for a character to unlock, but experienced players should be able to do it across the first two floors over a few attempts.
Azazel is an extremely powerful character for those who can wield him well. Rather than shooting tears, Azazel fires an energy beam at his opponents, which deals a lot of damage. He also flies and starts with The Fool card, allowing him to teleport to the start of a floor once. The downside is that the beam isn't very long, so Azazel will have to get close to his enemies to kill them, plus, he has no heart containers, instead starting with three Black Hearts.
Unlocking Azazel isn't much in the way of a challenge, but it does require some luck. Players who make three deals with the Devil in one run will unlock Azazel. This requires a Devil Room to spawn, likely more than once in a run, and players must have enough heart containers that they can sacrifice to take the deals.
Initially, Lazarus isn't that great of a character, having all-around worse stats than Isaac, and a pill of random effect. However, he starts with an extra life, and upon dying, transforms into Lazarus' Risen, who has only one heart container, but boosts in almost every stat.
Lazarus stands as one of the easiest characters to unlock, although it may take a bit of doing. Players need to have 4 Soul Hearts or Black Hearts at once. Soul Hearts aren't that hard to come by, but players will need to be careful about how much damage they take, as Soul Hearts are always lost first.
Eden is a mysterious character. Their stats aren't fixed, as everything about Eden (including their hairstyle) is randomly generated at the start of a run. Eden can spawn with anything from three red hearts to a single soul heart, and all of their stats can be both exceptional and terrible.
To unlock them, players must complete The Womb, meaning they must defeat Mom's Heart for the first time. Although this technically requires beating the final boss, the singular requirement makes Eden one of the easier characters to unlock.
The Lost has the exact same stats as Isaac, except they have no hearts. Not just red hearts, but any type of heart, they have zero health. This means that one hit from anything is instant death, and they cannot gain any type of heart either. They start with an Eternal D6, allowing players to reroll any items they get.
Before the Afterbirth DLC, unlocking The Lost was a long & complicated string of tasks. However, with that DLC, it became simpler (although still difficult). Players must die in a Sacrifice Room whilst holding the Missing Poster item to unlock it. Sounds simple, but unlocking the Missing Poster requires defeating The Lamb whilst playing as Isaac. The Lamb is a secret boss that can only be reached after defeating Satan five times whilst holding The Negative item.
Alternatively, if the player has enough hearts, hurting themselves on the spikes in a Sacrifice Room 12 times on the same floor, there will be a 50% chance that the player will be immediately teleported to the floor where The Lamb awaits. This 50% chance is rerolled for every hit on the spikes after the 12th.
Lillith is the first character added by one of the game's DLCs, and she has a unique play style. She is permanently afflicted with the Blindfolded condition, meaning she cannot fire tears. Instead, she must use her Incubus familiar to deal damage. She also starts with Cambion Conception, which spawns a new familiar after enough damage is taken; and the Box of Friends, which spawns a copy of every active familiar for the current room.
Unlocking Lilith requires beating Greed Mode whilst playing as Azazel. Greed Mode is a wave-based mode where players must defeat waves of enemies on seven different floors, before defeating a unique boss, known as Ultra Greed.
Keeper is one of the biggest challenges both in terms of their playstyle and how they're unlocked. Keeper uniquely spawns with Coin Hearts, which only heal when coins are picked up. By default, it is only two, but more can be unlocked by getting deep into the game with Keeper. As a benefit, they start with a triple shot.
Unlocking them is going to take a lot of work and once again centers around the game's Greed Mode. At the end of every Greed Mode run, once Ultra Greed is defeated, a donation machine appears, similar to the one in the shop. Players can deposit all their leftover coins into this machine, and it slowly unlocks upgrades for characters. In order to unlock Keeper, players must get the counter on this machine all the way up to 999, then deposit one more coin to overflow it back to zero.
Named after the angel known as "The Destroyer," Apollyon has a vastly different play style to most characters. His stats are identical to Isaac's. However, he spawns with The Void item. This consumes any items out on the floor, such as those in Treasure & Boss rooms. Consuming a passive item gives a random stat boost, but consuming an active item absorbs that effect. Then, when players use The Void, it will activate every effect it has absorbed.
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To unlock Apollyon, players must defeat Mega Satan. This extremely tough boss resides on the same floor as The Lamb, however, Mega Satan is behind the massive locked golden door on the floor's starting room. To unlock this door, players must combine two key pieces, which themselves are tough to unlock.
First, players must defeat The Lamb whilst playing as ??? to unlock them. Then, players must get two Angel Rooms, and defeat the Angel boss inside both of them (the fights are started by bombing the angel statue in the centre of the room). Take the two key pieces to Dark Room or Chest, the door will automatically unlock, defeat Mega Satan, and Apollyon will become a playable character.
The Forgotten is perhaps the strangest of all the playable characters, as it is actually two characters. When playing as The Forgotten, players will be controlling both that character and The Soul. The Forgotten does more damage and starts with two Bone Hearts, which take three hits to deplete, whilst The Soul only has a single Soul Heart. If The Soul dies, so does The Forgotten.
Unlocking this character is the most complicated of all (not counting The Lost pre-DLC), with secrets piled onto secrets. First, playing as any character, defeat the boss on the first floor in under a minute (a sound effect plays to indicate success), then go to the floor's starting room and it should be covered by the shadow of a shovel. Bomb anywhere in the room, and the Broken Shovel item will appear. This item causes Mom to continually try to stomp the player, so be careful.
Second, players must get to the Depths to defeat Mom in under 20 minutes, this unlocks the Boss Rush. Beat the Boss Rush and the second piece of the Broken Shovel will be given, forming Mom's Shovel. Next, get to the Dark Room floor and find the Grave Room, which should have a single patch of dirt in the middle. Use Mom's Shovel whilst standing on the dirt and The Forgotten will be unlocked.
Bethany is the first character from the Repentance DLC and sister to Lazarus. Stat-wise, she seems like a fairly normal character. She has three Red Hearts and standard stats in everything else. However, she can't pick up Soul or Black Hearts, as she uses them to charge her active items. She starts with one such item, the Book of Virtues. This spawns Wisps around the player that shoot tears at enemies but can be killed if they take enough hits.
Bethany is unlocked by playing on hard mode as Lazarus. Players must take the run all the way to Mom's Heart/It Lives and defeat it without losing a life. Lazarus is much weaker in his first life, so this will be quite the challenge.
The final unlockable character is another duo, but one more powerful than The Forgotten & The Soul. Jacob has three Red Hearts, above-average luck, shot speed & fire rate, but below-average damage. Esau has one Soul Heart & one Red Heart, below-average luck, shot speed & fire rate, but above average damage. Balancing this duo with items makes for a lot of interesting scenarios.
To unlock these characters, players must defeat Mother, one of the game's most gruesome-looking bosses. Note, this is NOT the same boss as Mom, who can be found in the Depths. Getting there is quite the gauntlet of tasks that must be completed through multiple runs.
First, players must get the "A Secret Exit" achievement. This is done by beating repentance bosses, Baby Plum, Reap Creep, and The Pile, which are regular bosses that can spawn in Basement or Depths. Once that is unlocked, a locked door will appear at the end of Basement, using a key will take players to Downpour. On one of those floors will be a room with a white fireplace, that transforms the players into The Lost when touched. Use this to enter the Mirrored World through a mirror, find the Treasure Room and collect Knife Piece 1.
Second, at the end of Downpour, another door will spawn that requires two bombs to get through. Doing so takes players to Mines. There, a room will spawn with a minecart on a broken track that leads to a boarded-up door. Find three yellow buttons on that floor and press them to repair the track, then touch the minecart. Inside the room will be Knife Piece 2, which combines to make Mom's Knife.
Third, at the end of Mines, a door will appear that costs two hearts to enter (The Lost can enter for free). This door leads to Mausoleum. Get to the end of this floor and defeat Mom, and a fleshy door will spawn. Stab it with the knife, and it will open. Inside, players must defeat Mom's Heart, and a room will open containing the entrance to Corpse.
Finally, progress to the end of Corpse, and the Mother fight will begin. This is a multi-stage fight, so be prepared, and defeating her will unlock Jacob & Esau.