|“||Then saith Jesus unto him, Get thee hence, Satan: for it is written, Thou shalt worship the Lord thy God, and him only shalt thou serve.||”|
Satan is the two-stage boss of Sheol, and one of the several final bosses of the game.
Satan is a large, muscular goat-like demon with few types of grey shading colors. He sports with such demonic features; including a pair of large, feathered wings, pupiless red eyes, long horns, a cross-shaped mark on the forehead, cloven hooves, and large fangs. He also wears a pair of torn brown pants.
In his second form, he seems to be incredibly huge with his bare legs only visible while stomping to attack Isaac.
As a statue, Satan look far less intimidating while sporting short horns, black eyes, and his baggy brown pants looks perfectly not torn at all.
Upon entering the Boss Room, Satan will summon The Fallen to fight the player. He behaves exactly like The Fallen anywhere else. However, a pair of Kamikaze Leeches also appear with him in the beginning of the fight.
This phase ends when the Fallen is killed, and will proceed to Satan's 1st form even if the leeches have not been destroyed.
An easy way to dodge his blood salvos is just standing behind the Satan Statue in the middle of the room, as The Fallen cannot fire through it. Otherwise, just follow the same tactics you would usually use for the Fallen.
When planting a Bomb about 3 seconds after entering the boss room where the Fallen appears (in front of the Satan statue), it should blow up the Kamikaze Leech, greatly damaging the Fallen and taking about a quarter of his health.
1st PhaseAfter defeating The Fallen, Satan comes out of the statue in the middle of the room and attacks the player. He has three attacks: firing two salvos of blood (first 5, then 4), firing a blood beam from his mouth (if his eyes are open before the attack), and firing a blood beam from each hand (if his eyes are closed before the attack). He only performs the latter two attacks if Isaac is standing directly in front of him.
One effective method of beating him is to stand on the very far left or very far right (occasionally switching if he gets too close) and dodging his projectiles while shooting at him. Focus more on dodging than where tears go (most will hit him). Note that while he is shooting his blood tears, he is incapable of firing his blood beams, so it's best to switch sides then.
Another tactic is simply to run in semi-circles around Satan, making sure not to stand still, while firing tears. This works best with a high Speed stat. Satan will continuously try to hit you (and ideally miss) with his blood bullets as you run around him.
After draining the health of his first form, Satan will fly off screen. He attacks solely by stomping the ground in the same fashion as Mom. He will stomp continuously with two legs faster than Mom's foot. In addition, he respawns 2 Kamikaze Leeches. By dropping any extra bombs you have while he is stomping, you can do decent damage to him and possibly chain react with the Kamikaze Leeches.
- Using The Bible during the fight against Satan will result in Isaac's instant death, unless he has The Wafer.
- To get an early hit on Satan's second form, place a bomb as he starts to laugh during the transition from phase one to phase two. Wait for the shadow to appear, then move away. The explosion should damage Satan.
- He was first added in the Halloween update for the original game.
- Satan's appearance is strongly reminiscent of Baphomet; the fictive deity that the Knights Templar were accused of worshiping.
- His pose as a statue form and from his V.S artwork is a nod to Baphomet's artwork as well.
- In the artbook, Satan's appearance look very different being less bulkier, possessing a smaller body, curly ram-like horns, and wings looking more leathery than feathered. His cross-shaped mark from his forehead is also missing.
- Satan's voice lines are from Mom, but played backwards and pitched down. This was hinted at by Edmund McMillen. 
- During the first phase, he says Mom's "ISAAC"-line in reversed with a deep-pitched voice.
- Also during the second phase, his reversed laughter is the same as Mom's when she hits Isaac with her arm.
- From the original game, he says Mom's "ISAAC"-line when transforming after defeating The Fallen. But in Rebirth, his quote plays at the beginning of the fight before summoning The Fallen.
- Satan can be fought after beating Mom the first time, by using The Joker Tarot card in The Womb 2. The Devil room contains a trapdoor leading to Sheol, bypassing the usual final boss Mom's Heart. If Isaac manage to beat Satan using this method, it'd count as Isaac have beaten the game twice instead of once, and he will unlock 2 endings/items instead of only 1. This also applies if Isaac manage to get the devil room after beating Mom's Heart for the first time then proceed to defeat him, with the additional benefit of giving Isaac 3 endings instead of 2.
- Satan's name could be named after one of the Nibbler enemies from Gish, one of Edmund's previous games.
- From the original game, the cross from Satan's forehead is inverted. But in Rebirth, the cross mark is perfectly downside up.
- As a statue from the original game, Satan's cross mark is missing.
- His animation while transforming from a statue to his living form in both the original game and Rebirth are different. From the original game, he bared his teeth and black aura forms while transforming. In Rebirth, his eyes turn red and smiles evilly with no black aura displaying.
"Moms Knife" - Defeat Satan with Isaac.
"The Guardian Angel" - Defeat Satan with Maggy.
"The Bomb Bag" - Defeat Satan with Cain.
"The Monster Manual" - Defeat Satan with Judas.
"The Demon Baby" - Defeat Satan with Eve.
"Forget Me Now" - Defeat Satan with ???.
"Blood Rights" - Defeat Satan with Samson.