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Spiders are enemies first added in the Wrath of the Lamb DLC for the original game, and also appear in the Rebirth remake. They can be found on every alternate floor from the expansion (Cellar, Catacombs, Necropolis, Utero), as well as The Chest from the original game.
Spiders move very quickly and will go in all directions randomly, making them unpredictable. However, if they have a direct line of sight on Isaac, and are close enough, they will move towards him.
Due to their small size, they can even fit between the corners of some rocks. As such, it's best to stay as far from them as possible.
- Outside of combat, 2 Spiders can occasionally spawn from a Red Chest and will always be spawned if Isaac blew up a Devil Beggar.
- When blowing up the Shopkeeper, 2 Spiders has a chance to be spawned.
- A pair of Spiders can be spawned after killing the Big Spider.
- Besides naturally spawning in some rooms, Spiders are also spawned when fighting Sacks, Widow, The Husk, The Wretched, Super Sloth (2 at once) and when destroying the smallest part of the Teratoma (also 2 at once).
- In Rebirth, Spiders can be also spawned by The Adversary.
- In Rebirth, they will spawn from blowing up vases.
- In Rebirth, they can be spawned by numerous enemies such as Nests and larger versions of Baby Long Legs.
- In the Afterbirth expansion, they can be spawned by Black Globin's Body.
- All Spiders only have four legs instead of eight. Edmund has acknowledged this by joking that he doesn't know how Spiders work.
- They are based off Tektikes from The Legend of Zelda.
- Just like all type of Flies, Spiders don't have champion variants.