First time both Leon and Chris would share starring roles in a Resident Evil game.
The logo was almost changed as some fans starting seeing a giraffe forcing a limbless human body to give it fellatio. Capcom acknowledged this by tweeting the word "giraffe. "
This is the first Resident Evil game to be rated M for Mature partially for nudity.
This game contains many references or homages the older games. These are Leon and Sherry getting separated by an exploding truck (in RE 2 Leon and Claire get separated by an exploding truck), Ada saves a Leon by giving him a key to a vehicle (in RE 4 Ada gives Leon a key to a jet ski), Chris battles a giant snake (he fought a giant snake in the first game), In certain areas the camera will changed to a fixed camera angle (the originals had a fixed camera angle gameplay ), and many others.
Despite what many think, this is in fact the second Resident Evil game where you can walk and shoot. You can walk and shoot in Resident Evil Outbreak 2, which came out 8 years before this.