For those well-versed with the Bible and other things, they'll enjoy the references to the stuff they know of.
- When under the effects of Whore of Babylon, your character leaves a small puddle of blood rather than the usual puddle of pee left at low health every time you enter a room. This may be a reference to past conceptions of what periods were (a curse due to Eve's actions of original sin) or even to the Biblical passage introducing the Whore of Babylon, "...and I saw a woman sit upon a scarlet coloured beast..."
- Azazel is a fairly commonly referenced demonic name. But it's also a word for a sacrificial scapegoat
— Azazel, like Isaac himself, is named after a sacrifice. - Skatole as an item makes flies less hostile towards you. In real life, it's a compound that in high concentrations has a faecal smell (though at lower concentrations it smells flowery). Since some types of fly feed on poop, it makes sense that Skatole would make Isaac more attractive to flies.
- Many items and enemies are named after medical conditions. Some of them, such as Teratoma and Fistula, are obscure enough to qualify as this.
- The Steam Achievement description for Jacob and Esau is "You are just like your father..." Although also a reference to the preceding cutscene (the unlock for Jacob and Esau is beating Mother), in the Bible, the father of Jacob and Esau is... Isaac.
- Akeldama, which is unlocked by Judas after defeating Mother, is a pile of entrails that lets Isaac leave a trail of bloody tears that hit foes. It's a reference to Judas' suicide in The Bible: he hung himself in Akeldama, and when he died, his organs spilled out of his body.
- Also in Book of Genesis, there's the story of how Jacob tricked Esau by offering him a delicious stew in exchange for the birthright to their dying father's possessions. In the game, Red Stew gives a short-term benefit (refills health and provides a great, but temporary, damage boost), while Birthright has a different permanent effect depending on the character that picks it up. In the case of Jacob and Esau, the one who picks it up copies three of the other's passive items. Tainted Jacob's Birthright effect goes even further with the reference; its pickup text is "It's not yours", and its effect duplicates Dark Esau, arguably benefiting him more than the player.
