The plague has traveled around the world infecting most of the world's population, turning everyone into the walking undead. The deadly virus also has destroyed the world as we knew it, rendering the planet a desert. Alice (Milla Jovovich) has been forced to roam the Earth alone attempting to stay off Umbrella's radar. A convoy led by Claire Redfield (Ali Larter) and former U.B.C.S. agent Carlos Olivera (Oded Fehr) along with L.J. (Mike Epps) and other survivors, who have not been infected, travel from small town to small town in search of other survivors and supplies, staying away from any large cities - areas that may potentially be infested with zombies. Their goal is to find a place that has not been infected by the virus.
As the film progress we see that Alice's powers have undergone substantial growth. Alice, after saving the convoy from a swarm of ravenous birds, joins the others in the hunt for a place to call home. Umbrella, on the other hand, has been forced to go underground. Dr. Isaacs (Iain Glen) has been conducting research at one such institution. This time, though, instead of developing a new viral creature, he is searching for a cure; a new serum that, in previous experiments, produce a subdued creature, one that has reasoning skills and vague memories, but if angered, will fly into a blind rage and devour any human unlucky enough to be in close proximity.
Dr. Isaacs had been using clones of Alice, running each through a rigorous simulation of the past situations Alice had been in, hoping to find the one with the same capabilities, therefore the same blood as the original. Unfortunately for the convoy, Dr. Isaacs finds Alice and tries to capture her in Las Vegas, after Alice persuades the convoy to journey to Alaska where Alice believes there lives an uninfected community, so he can continue his experiments. Alice and the others, this time face not normal zombies, but instead the new enraged zombies. Dr. Isaacs goes with the strike team during the operation, and in taking this action, he seals his own fate when he is bitten by his new creation while trying to make an escape. Upon returning to his underground lab, Dr. Isaacs injects himself several times with the anti-virus, turning him self into a new creature, a self-regenerating mutant with tentacles that can extend out an infinite length, capable of pursuing human flesh.
