Resident Evil Extinction

The film begins with Alice (Milla Jovovich) waking up at the hospital, just like the end of the first Resident Evil. Alice defeats the usual obstacles, including the laser room, though she is eventually killed. Her body is taken outside and dumped into a pit. The pit is then shown to be filled with hundreds of Alice Clones. The camera zooms out from the facility's camouflaged entrance, made to look like a shack (the rest of the facility is underground). The shack is surrounded by a high fence and hundreds of zombies.

Five years after the T-virus escaped Raccoon City, it has spread around the world. As organisms are infected, the environment becomes destroyed. Alicewanders the desert wastelands of the South-Western US. Dr. Sam Isaacs considers Alice's re-capture a top priority since she has the ability to bond with the T-Virus. He tries to persuade the Umbrella board that he can use her blood to develop a permanent cure, as well as tame the infected. The new Umbrella chairman Albert Wesker (Jason O'Mara) orders Isaacs to instead use the clones to create a cure and he refuses to authorize Alice's recapture until they are sure of her location.

Meanwhile, Claire Redfield's (Ali Larter) convoy, which includes the Raccoon City survivors Carlos Olivera (Oded Fehr) and L.J. (Mike Epps), along with new survivors K-Mart (Spencer Locke), Mikey (Christopher Egan), Chase (Linden Ashby) and Nurse Betty (Ashanti Douglas) along with others, travel cross country. While searching a motel for supplies, L.J. is bitten. The next morning the convoy is attacked by infected crows. The crows almost overpower the convoy, killing Nurse Betty and taking out the flamethrower operator causing the weapon to careen out of control. Alice appears and saves Carlos and others from a fiery death. She uses her psionic powers to cover the sky with a blanket of fire, killing the crows. Alice is introduced to Claire, and gives her a diary she found. The book claims of a 'safe zone' in Alaska. Alice and Carlos convince Claire to take her convoy to Alaska. They agree to go to Las Vegas to search for supplies for their trip to Alaska.

Dr. Isaacs' attempts to domesticate the infected have led to a new zombie breed. Wesker's security officer, Captain Slater (Matthew Marsden), is adamant about Isaacs not disregarding Umbrella's regulations. Slater does admit that the "super zombies" (the Crimson Heads) would be useful, but reiterates that Isaacs is out of control.

Umbrella triangulates Alice's location based on her psionic abilities. Dr. Isaacs has a crate of his new zombies sent to ambush the convoy, against Wesker's specific orders. Carlos gets infected by L.J., and most of the convoy, including Chase and Mikey, are killed in the ambush. Umbrella tries to shut Alice down remotely, She breaks free from their programming and continues to fight. She finds Isaacs at the scene, and becomes infected as he tries to flee. Alice and K-Mart use Isaacs' computer to track the helicopter's flight path, leading to Umbrella's underground location.

The convoy goes to the site, which is surrounded by zombies. Carlos sacrifices himself by plowing his truck into the zombie mob and blowing them all up, giving Alice and Claire time to load survivors into the helicopter. Alice decides to stay behind. Ordered by Wesker to liquidate Isaacs, Slater finds the scientist locked in his lab, injecting himself with massive doses of Anti-Virus in an attempt to counter-act the infection. Slater shoots Dr. Isaacs, triggering his mutation into a Tyrant. Isaacs kills all the facility employees, but is confined to the lab's lower levels.

• Milla Jovovich as Alice and the clones: The primary protagonist
• Ali Larter as Claire Redfield: 
• Oded Fehr as Carlos Olivera: Ex-U.B.C.S. soldier
• Iain Glen as Dr. Sam Isaacs: The primary antagonist, and head scientist of the North American facility. 
• Ashanti Douglas as Nurse Betty: A tough young woman who acts as the medical unit in Claire's convoy. 
• Christopher Egan as Mikey: A young mature computer junkie who drives the "computer station" portion of the convoy
• Spencer Locke as K-Mart: A girl found by Claire's companions hiding out in a K-Mart store prior to the outbreak.
• Matthew Marsden as Captain Slater
• Linden Ashby as Chase
• Jason O'Mara as Albert Wesker: Based on the video game character of the same name
• Mike Epps as L.J. Wayne: Former citizen of Raccoon City
• Madeline Carroll as White Queen: The sister Artificial Intelligence of the original Red Queen