The Binding of Isaac: Rebirth is the ultimate roguelike for item synergy enthusiasts — over 700 items that combine in thousands of emergent ways, many of which the developers never explicitly designed. One run you're firing homing lasers, the next you're spawning an army of familiars, and the next you're a ball of knife-shooting orbital meat. The game's depth is staggering: 34 playable characters (including Tainted variants), 12 endings, secret floors, challenge runs, and an item pool so vast it takes hundreds of hours to see everything. The Repentance expansion is considered the definitive version, adding two new characters, hundreds of items, and the hardest content in the game.
Picking the right build determines how your experience plays out. These builds are ranked by overall effectiveness — factoring in damage, survivability, gear requirements, and how well they scale into endgame.
Quick Rankings
| Build | Tier | Playstyle | Core Gear |
|---|---|---|---|
| Isaac | A | Use the D6 to reroll bad items into good ones. Prioritize tear modifiers (Brimstone, Tech X) and damage ups. Isaac can become anything based on what the D6 generates. | D6 (starting item), any strong tear modifier, health upgrades |
| Azazel | S | Fly over obstacles and hazards, charge Brimstone, and sweep the room. Range upgrades are the highest priority since they extend Brimstone's reach dramatically. | Starting Brimstone, any range up, any damage up |
| Judas | S | Activate Book of Belial before boss rooms for guaranteed Devil Deals and +2 damage. Play aggressively since your high damage kills enemies before they can threaten your low HP. | Book of Belial, devil deal items, damage multipliers |
| The Lost | B | Never get hit. Take every Devil Deal for free. Holy Mantle gives you one hit of protection per room — use it as insurance, not as a crutch. | Holy Mantle (unlocked through Greed Mode), free devil deal items, flight |
| Tainted Characters | varies | Each Tainted character demands a unique strategy — Tainted Keeper must spend coins to survive, Tainted Bethany uses soul hearts as spell charges, Tainted Jacob is chased by Dark Esau. | Varies dramatically per tainted character |
A-Tier: Isaac
Isaac is the default character with balanced stats and the D6 active item — the most important item in the game. The D6 rerolls pedestal items, letting you cycle bad items into good ones. Isaac's flexibility comes from being able to shape his run through strategic rerolling. He has no weaknesses but no starting advantages either.
Core Setup
| Slot | Choice | Why |
|---|---|---|
| Primary Equipment | Brimstone | A charged beam that pierces all enemies and deals massive damage. |
| Core Gear | D6 (starting item), any strong tear modifier, health upgrades | Maximizes build potential |
| Stat Priority | Tears (fire rate), damage, range | Optimal scaling |
| Key Mechanic | item synergies | Items modify your tears (projectiles) in stackable ways. |
How to Play Isaac
Use the D6 to reroll bad items into good ones. Prioritize tear modifiers (Brimstone, Tech X) and damage ups. Isaac can become anything based on what the D6 generates.
Isaac is the default character with balanced stats and the D6 active item — the most important item in the game. The D6 rerolls pedestal items, letting you cycle bad items into good ones. Isaac's flexibility comes from being able to shape his run through strategic rerolling. He has no weaknesses but no starting advantages either.
What makes this build work: The synergy between Brimstone and item synergies creates a gameplay loop that outperforms other options. Core gear like D6 (starting item), any strong tear modifier, health upgrades amplifies this further.
Pros:
- Highest overall performance
- Clear stat priority (Tears (fire rate), damage, range) makes gearing straightforward
- Works in all content types
Cons:
- Popular pick, resources may be contested
- Needs specific gear to reach full potential
S-Tier: Azazel
Azazel starts with a short-range Brimstone beam and flight — two of the strongest abilities in the game, for free. His Brimstone clears rooms instantly in the early floors. The only downside is the short beam range. Azazel is the best character for unlocking completion marks and learning the game.
Core Setup
| Slot | Choice | Why |
|---|---|---|
| Primary Equipment | Mom's Knife | Replaces tears with a thrown knife that deals 2x your damage on contact and 6x on point-blank throw. |
| Core Gear | Starting Brimstone, any range up, any damage up | Maximizes build potential |
| Stat Priority | Range (extends Brimstone), damage, speed | Optimal scaling |
| Key Mechanic | character unlocks | Characters unlock by completing specific achievements. |
How to Play Azazel
Fly over obstacles and hazards, charge Brimstone, and sweep the room. Range upgrades are the highest priority since they extend Brimstone's reach dramatically.
Azazel starts with a short-range Brimstone beam and flight — two of the strongest abilities in the game, for free. His Brimstone clears rooms instantly in the early floors. The only downside is the short beam range. Azazel is the best character for unlocking completion marks and learning the game.
What makes this build work: The synergy between Mom's Knife and character unlocks creates a gameplay loop that offers reliable performance. Core gear like Starting Brimstone, any range up, any damage up amplifies this further.
Pros:
- Most versatile option
- Clear stat priority (Range (extends Brimstone), damage, speed) makes gearing straightforward
- Works in all content types
Cons:
- Lower peak damage than S-tier
- Needs specific gear to reach full potential
S-Tier: Judas
Judas starts with the highest damage multiplier (1.35x) and the Book of Belial (+2 damage when activated, also increases Devil Room chance). He has only 1 red heart, making him a glass cannon. With Book of Belial active, Judas outdamages every other character. Devil deals are easy to access due to Book of Belial's bonus.
Core Setup
| Slot | Choice | Why |
|---|---|---|
| Primary Equipment | Sacred Heart | An Angel Room item that grants +1 damage, homing tears, and a 2. |
| Core Gear | Book of Belial, devil deal items, damage multipliers | Maximizes build potential |
| Stat Priority | Damage (already high), soul hearts for survivability, speed | Optimal scaling |
| Key Mechanic | room clearing | Each floor consists of rooms cleared by defeating all enemies. |
How to Play Judas
Activate Book of Belial before boss rooms for guaranteed Devil Deals and +2 damage. Play aggressively since your high damage kills enemies before they can threaten your low HP.
Judas starts with the highest damage multiplier (1.35x) and the Book of Belial (+2 damage when activated, also increases Devil Room chance). He has only 1 red heart, making him a glass cannon. With Book of Belial active, Judas outdamages every other character. Devil deals are easy to access due to Book of Belial's bonus.
What makes this build work: The synergy between Sacred Heart and room clearing creates a gameplay loop that offers reliable performance. Core gear like Book of Belial, devil deal items, damage multipliers amplifies this further.
Pros:
- Best survivability
- Clear stat priority (Damage (already high), soul hearts for survivability, speed) makes gearing straightforward
- Works in all content types
Cons:
- Slower clear speeds
- Needs specific gear to reach full potential
B-Tier: The Lost
The Lost has no HP — any damage kills instantly (unless you have Holy Mantle, which blocks one hit per room). The tradeoff is access to all Devil Deal items for free and flight from the start. The Lost is the ultimate high-risk character — incredible power potential but zero margin for error. Unlocking all Lost completion marks is a badge of honor.
Core Setup
| Slot | Choice | Why |
|---|---|---|
| Primary Equipment | Godhead | An Angel Room item exclusive to The Lost's completion marks. |
| Core Gear | Holy Mantle (unlocked through Greed Mode), free devil deal items, flight | Maximizes build potential |
| Stat Priority | Holy Mantle (mandatory), damage, tears | Optimal scaling |
| Key Mechanic | devil and angel deals | After beating a floor boss, a door may appear leading to a Devil Room (powerful offensive items that cost red hearts) or Angel Room (powerful defensive items for free). |
How to Play The Lost
Never get hit. Take every Devil Deal for free. Holy Mantle gives you one hit of protection per room — use it as insurance, not as a crutch.
The Lost has no HP — any damage kills instantly (unless you have Holy Mantle, which blocks one hit per room). The tradeoff is access to all Devil Deal items for free and flight from the start. The Lost is the ultimate high-risk character — incredible power potential but zero margin for error. Unlocking all Lost completion marks is a badge of honor.
What makes this build work: The synergy between Godhead and devil and angel deals creates a gameplay loop that provides a unique approach. Core gear like Holy Mantle (unlocked through Greed Mode), free devil deal items, flight amplifies this further.
Pros:
- Strong in group/team content
- Clear stat priority (Holy Mantle (mandatory), damage, tears) makes gearing straightforward
- Excels in its niche
Cons:
- Weaker solo performance
- Requires deep game knowledge
varies-Tier: Tainted Characters
Repentance adds 17 Tainted variants of each character with radically different mechanics. Tainted Isaac has limited item slots. Tainted Cain crafts items from pickups. Tainted Lazarus alternates between two forms each room. Tainted Lost has Holy Mantle but can only get 'better' quality items. These are the endgame challenge characters.
Core Setup
| Slot | Choice | Why |
|---|---|---|
| Primary Equipment | Tech X | Replaces tears with a chargeable ring of energy that scales in size with charge time. |
| Core Gear | Varies dramatically per tainted character | Maximizes build potential |
| Stat Priority | Varies per character | Optimal scaling |
| Key Mechanic | boss rush | Reaching Mom's boss room within 20 minutes triggers Boss Rush — a gauntlet of 15 boss waves that rewards a powerful item. |
How to Play Tainted Characters
Each Tainted character demands a unique strategy — Tainted Keeper must spend coins to survive, Tainted Bethany uses soul hearts as spell charges, Tainted Jacob is chased by Dark Esau.
Repentance adds 17 Tainted variants of each character with radically different mechanics. Tainted Isaac has limited item slots. Tainted Cain crafts items from pickups. Tainted Lazarus alternates between two forms each room. Tainted Lost has Holy Mantle but can only get 'better' quality items. These are the endgame challenge characters.
What makes this build work: The synergy between Tech X and boss rush creates a gameplay loop that provides a unique approach. Core gear like Varies dramatically per tainted character amplifies this further.
Pros:
- Unique, rewarding playstyle
- Clear stat priority (Varies per character) makes gearing straightforward
- Excels in its niche
Cons:
- High skill floor, punishing when misplayed
- Requires deep game knowledge
Build Progression Path
- Start with Azazel — the most forgiving option for learning the game
- Transition to Isaac once you understand core mechanics and have access to Brimstone
- Keep a Judas setup for content that keeps killing you
- Try Tainted Characters for a fresh experience once you've mastered the basics
Gearing Tips
- Invest in your primary equipment first — it gives the biggest power spike
- Tinted rocks (slightly discolored rocks with an X mark) always contain soul hearts, black hearts, or bone hearts when bombed. Learn to spot them — they're one of the most reliable health sources in the game.
- Secret rooms always border at least 3 rooms (including non-accessible rooms). Bomb walls between rooms that share borders with many adjacent rooms. Use the map to identify the most probable secret room location.
- Don't spread upgrade resources across multiple builds until endgame
See our tier list for current meta rankings, or the beginner's guide if you're just getting started.
