Knights are children with their bodies covered completely in iron, and a mask with two black eyes and a mouth. Their brain is the only part not covered in armor.
Knights are invincible from the front, and can only be damaged from the back or, occasionally, the side.
Knights generally move about the room erratically, but react to having orthogonal line-of-sight on the player. If the player gets close enough to a Knight on a horizontal or vertical path, the Knight will change direction to move towards the player. The Knight will be set in this new direction until it hits an obstacle. This means that attracting a Knight's attention, and then quickly moving behind it to shoot can be a viable strategy, especially with a high Speed stat and when done horizontally in rooms with few obstacles. The Knight's line of sight is limited, however, which can allow the player to shoot a Knight vertically across the room without the Knight changing direction if on opposite ends. Care should be used in fighting large numbers of them, especially in the more maze-like room layouts.
Knights can be safely dispatched with the use of piercing shots from Cupid's Arrow, Technology, or Brimstone, as these will damage them even from the front. The player can also use Bombs, or if the The Ladder or flight ability (from Lord Of The Pit or Transcendence ) is available, simply hiding safely over a pit and shooting from a distance. Knights will also take damage from walking into Fireplaces or Spikes. Status effect tears, such as The Common Cold can be applied from the front. You can also hold Mom's Knife to kill Knights, if you're not worried about taking damage.
Using Mom's Pad will sometimes reverse the hit spot on the Knights meaning the player has to fire at the Metal face on the Knight whereas the brain seems to react like it is the Metal face.
Selfless Knights have a mouth wide agape similar to a Maw's expression and Isaac's face on the back of their heads. They behave just like regular Knights, except they advance towards Isaac at a higher speed if detected. They are commonly found in Sheol, but will occasionally replace regular Knights as champion version in previous floors, where killing them will drop a Pick Up. They are very rarely found in areas all the way up to the Caves/Catacombs.
- Edmund has stated that Knights are a reference to Darknuts from The Legend of Zelda series, which can also only be harmed the same way.