Mom's Hands are a reference to Wallmasters from The Legend of Zelda.
Death's Head was likely inspired by Bubbles from The Legend of Zelda on the NES, as they are both skulls that are invulnerable and maneuver by bouncing off walls.
Scolex may have been inspired by Lanmola from The Legend of Zelda: A Link To The Past, both being underground and surfacing to attack before returning underground.
The original flash version of The Binding of Isaac uses a HUD that is a nearly direct port of the original NES Zelda title's HUD.
Coins, Keys, and Bombs are used similarly to Rupees, Keys, and Bombs in the NES game.
The general gameplay is a reference to the original NES title, right down to the hud.
'M (Reference to a glitch in pokemon: Red and Blue).
TMTRAINER (Reference to a glitch in Pokemon: Red and Blue).
Poke Go (Reference to the mobile game Pokémon Go).
(Reference to the infamous Missing No glitch from the first generation of Pokémon games)
Friendly Ball - (The item is a reference to Poké Balls from the Pokémon franchise.).
Mega Mush - I'm a Big Boy Now (Reference to the Mega Mushroom power-up).
Mini Mush - Speed + range up (Reference to the Mini Mushroom power-up).
Magic Mushroom - All stats up! (Reference to the Super Mushroom power-up).
Liberty Cap - Touch fuzzy, get dizzy (Reference to level 1-7 in the Super Nintendo title Yoshi's Island).
(The cover looks like the NES Super Mario Bros.
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How to Jump - It's time you learned how.
Gnawed Leaf - Turn into an invincible statue (The item's appearance is a reference to the Leaf power-up, the effect to the Tanooki suit power-up from Super Mario Bros.
Bobby-Bomb - Homing bombs (Reference to the Bob-omb enemy from the Mario series).
1up! - Extra Life (Reference to the 1up power-up).
The Gamekid - Reference to Pacman and the Nintendo Gameboy.
Lil Spewer - The protagonist of Edmund's 2009 game, Spewer.
Triachnid - The protagonist of Edmund's 2006 game, Tri-achnid.
Steven - The protagonist of Edmund's 2009 game, Time Fcuk.
Steven - Attaches a small head to Isaac, similar to the smaller Steven from Time Fcuk.
Little Steven - A reference to the smaller Steven from Time Fcuk.
Sisters Vis - A boss of Edmund's 2004 game, Gish.
Little Gish - A familiar based off of Gish.
Gish - The protagonist of Edmund's 2004 game, Gish.
Clots - Enemies that appear to be smaller versions of Gish.
Ball of Tar - Gives Isaac an appearance similar to that of Gish.
SMB Super Fan - (Gives Isaac an appearance similar to Super Meat Boy).
shrinking after his defeat in Super Meat Boy).
Cube of Meat - (Becomes Super Meat Boy).
Ball of Bandages - Gotta lick 'em all! (Becomes Bandage Girl from Super Meat Boy).