Leon appears to have short brown hair, with fringes on each side and brown eyes. In the FMV scenes in Resident Evil 2, his brown hair becomes a copper shade and his eyes turn blue. From Resident Evil: Vendetta through the remake version of Resident Evil 4, he is depicted to have dark brown hair and ice blue eyes.

Ada Wong is a striking Asian-American woman of Chinese descent, sporting a sleek figure and graceful mannerisms. She fits the archetype of the stylish and beautiful assassin or "femme fatale". For the most part, Ada's physical appearance has not changed much over the course of the series. She usually sports short black hair in the same style and her eye color is the only thing that has changed once. In Resident Evil 4 they were a clear, almost green shade but in all other appearances her eyes are shown to be brown. Ada's main outfits have usually consisted of red and black, those being her most prominent colors. In the remake version, her short hair is now styled as a short bob.

Claire has long auburn hair tied to a ponytail and blue eyes. Claire's original outfit in Resident Evil 2 consisted of a black short-sleeved, short-legged cycling skinsuit worn under a pink vest with a "Made in Heaven" design on the back (which she gave it to Sherry at the end of the game), pink-colored jean shorts, brown boots, and black riding gloves. Her special outfit in the game consists of a leather jacket and pants with a "Let Me Live" design on the back and a red bandanna.

Chris was developed to be the typical "tough guy" type, commonly found in action movies: handsome, spiked hair, bare muscular build and likes combat knives. The color of his hair is naturally brown in some FMV scenes and his CGI appearance from the current games until the end of Resident Evil 6.

In most promotional artworks and CGI appearances, Ethan is depicted not to shown his real face. He has neatly short pale brown hair and brown eyes after his real face was briefly shown.

Rosemary Winters appears as a 16-year-old teenager with dirty blonde hair, sky blue eyes, and fair skin

Bryan is a young caucasian man who's presumably in his mid to late 20s. He has messy, blonde-brown hair with bangs that fall across his forehead. He also has a stubble of a mustache and beard.