The Binding of Isaac has always sought to crush players at every turn. First released in 2011 as a Flash game, Isaac has come a long way from his grassroots origins. The original title contained only 100 items, but now that creator Edmund McMillen has graced the community with the final DLC Repentance, that total now stands at over 700. All this can seem intimidating, but there are ways to conquer this brutal experience.
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Items are unlocked in The Binding of Isaac by playing the game through to the end. Repentance now features 34 characters to play. Beating the game or certain challenges with each character will unlock new items that can be found in subsequent playthroughs. The game becomes much easier when you have a hoard of powerful items to chance upon. It can seem like luck is the only determining factor to a successful run to a new player. Luck is a big part of any Isaac build, but strategy can be employed just as often to force a favorable outcome.
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It can be argued that any run graced with Brimstone is a win already. This build, however, has something very special going for it. With Tiny Planet and Brimstone, Isaac will shoot a laser that forms a ring around his body. This is cool enough, but Lost Contact ties this build up. Lost Contact destroys enemy projectiles in contact with Isaac's tears. In this case, every time Isaac shoots, he will create a wall of damage that almost completely protects him from enemy shots.
This build is especially fun because of the few items needed to build it. Any other items collected will only improve the build.
9 Tanuki Terror: Gnawed Leaf, Any Damaging Orbital
Most people think that hyper-offense is the way to go when chugging through such a brilliant, brutal Roguelike. Isaac can be played very defensively too, though. That is the essence of this simple but terrifyingly effective build. Gnawed Leaf turns Isaac into an immobile and invincible statue, as long as he neither moves nor shoots. On its own, this effect is useless, as Isaac can not inflict or deal damage.
However, add a damaging orbital of choice (i.e. Attack Fly, Cube of Meat, Sacrificial Dagger) and you will see how broken this build is. The strategy simply revolves around putting Isaac within orbital range of enemies and standing still. That's it. Isaac just stands there while his orbital takes care of all the dirty work. To speed up room clearing, try making a level four Bandage Girl or Super Meat Boy.
8 High Roller: Blank Card, Two of Diamonds, Shop Refresh, Battery
A complicated build but always a winner. First, find the Blank Card item, which mimics the effect of a tarot card Isaac is holding. Next, find a Two of Diamonds tarot card, which doubles Isaac's held coins. Finally, find Shop Refresh, which makes all items in the shop come back after being purchased.
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With those in hand, Isaac simply needs to find a Shop that sells a battery, and Blank Card can be used to double his coins endlessly. In other words, Issac has infinite money, and every time he touches an item in the Shop, a new one will take its place. This can allow Isaac to spawn every item in the game in a single room, given enough patience. This can be a great way to test out all the new items Repentence has to offer.
7 Plagued: Polyphemus, Sinus Infection, Toxic Shock, Contagion
Poison is an underrated effect in The Binding of Isaac. Poison deals damage to enemies equal to Isaac's tear damage per proc. In other words, each poison tick on an enemy will be damaged as if they were hit by a tear. Toxic Shock's effect is simple: Upon entering a new room, all enemies with automatically be poisoned. Contagion makes enemies blow up, poisoning other enemies nearby for a chain reaction.
With Polyphemus, Isaac's poison will kill almost all enemies every time a room is entered. If Sinus Infection cannot be obtained, try collecting some trinkets to round out your damage.
6 Health Generator: Serpent's Kiss, Maw of the Void, Toxic Shock, Tooth and Nail
One of the biggest obstacles to any Isaac run is a low health pool. This build basically ensures immortality. Serpent's Kiss makes enemies drop black hearts when they die from poison damage. Maw of the Void spawns black hearts when enemies die from the black ring.
Tooth and Nail makes Isaac invincible for one second every five seconds. This, combined with Serpent's Kiss' poison-on-damage effect, will spawn dozens of black hearts per floor. Keep in mind that Isaac needs to have as few red hearts as possible to make this build a success.
5 Bombs, Bombs Everywhere: Monstro's Lung, Dr. Fetus, Scatter Bombs, Pyromaniac
This is the flip side of the previous build. You want to have as many red hearts as possible for this one. Pyromaniac will replenish red health for Isaac if he is hit by an explosion. Monstro's Lung, Dr. Fetus, and Scatter Bombs will practically fill every room with active bombs.
This means that Isaac is always close to health replenishment with this build. It also ensures that Isaac cannot die as long as he continues shooting. This build can be combined with any bomb upgrades to really make it shine.
4 Instant Victory: Plan C, Lazarus Rags
This method is niche but still effective in the right hands. These two items can put a quick end to any boss. Plan C instantly kills all enemies in a room, including bosses. This would be great if not for the fact that Isaac is also instantly killed.
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Enter Lazarus Rags. This will respawn Isaac in the same room he just died in, effectively bypassing the negative effects of Plan C. Do note that this interaction is quirky. Any boss with a death animation longer than three seconds will give credit for the kill to Lazarus instead of the character the player chose.
3 Flock Leader: Box of Friends, Quints, All Familiars
A classic Lilith favorite, this build centers around collecting as many familiar items as possible. The effect of Quints is that dead enemies spawn a random familiar that shoots towards other enemies. Box of Friends doubles the current familiars. Combine this with as many familiars as possible in a run, and Isaac can focus on dodging while his friends do the heavy lifting.
Familiars are a common sight in every item pool in the game, so this can be an attractive build for most characters' success.
2 Spacebar: Tammy's Head, Brimstone
Tammy's Head is an often overlooked item. Most players will pass it up in hopes of something better. Those in the know, however, will hold on to it in hopes of creating this synergy. This build is named Spacebar, because that's the only key PC players will need for the rest of the run. Tammy's Head recharges every room. With Brimstone in the equation, it will fire ten brimstone lasers in every direction. Every room. This is the game on easy mode.
This is a great build for new players, as these two items are part of the original item pool and can be found together often.
1 Far And Away: Continuum, Lump of Coal, Ouija Board
Continuum is a unique item that lets Isaac's tears travel past the bounds of the board and wrap back to the other side. Lump of Coal synergizes well with this, adding damage to tears as long as they fly. Ouija Board is an example of an item that would work here, but an item that gives spectral or piercing tears is a substitute.
Isaac can fire in any direction, and his tears will travel almost endlessly, picking up damage the longer they travel. To make this run a success, do everything in your power to collect range upgrades.
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