Two of the characters in the game, gun shop owner Robert Kendo, and police officer Marvin Branagh, originally had much larger parts in Resident Evil 1.5, with Robert Kendo (Originally named "John") helping Elza Walker out and Marvin accompanying Leon and Ada throughout his story. At one point in 1.5, it appears that Marvin, rather than Sherry in the final game, is infected with a virus and the player has to get him a cure.

In the final game, both die fairly early on, and the player even has to kill a zombified Marvin in their character's "A" scenario.

Tofu from the secret game mode Tofu Survivor was originally created as a means to test the game's collision detection during development. He later got his own mode as a parody of HUNK's 4th Survivor.

There is an easter egg that allows you to shoot bullet holes in the screen anytime your character is facing the camera.

Originally, the female lead character was supposed to be Elza Walker. When Resident Evil 2 was made again, she was replaced by Claire Redfield. Elza's only appearance was in Resident Evil 1.5.

The S.T.A.R.S. office is way too small for a team of 12 and for some reason only has the desks of Barry, Chris, Jill, Rebecca and Wesker. They may have made some changes after the Mansion Incident but Brad's desk is missing and he had still been alive at the time the office was last used.

The renowned director of zombie movies, George A. Romero, made the original live-action commercials for Resident Evil 2. He was later supposed to direct the live-action Resident Evil movies, but the deal was given to Paul W.S. Anderson.