Somewhere below Raccoon City resides a complex known as the Hive. Run by the powerful Umbrella Corporation - a leading supplier of computer technology and medical and health care products - the Hive is home for more than 500 researchers and scientists who work on covert operations involving military technology, medical experimentation and bio-weaponry.
Overseen by a powerful supercomputer known as the Red Queen (voice of MICHAELA DICKER), things seem fine in the Hive until one of their latest projects - known as the T-virus - goes awry. Accordingly, the Red Queen puts the place in lockdown and uses nerve gas to kill everyone inside, all to prevent the now airborne virus from escaping the facility.
Meanwhile, in a manor above one of the secret entrances to the Hive, Alice (MILLA JOVOVICH) is waking up in the shower, unaware of her identity or location. After discovering that she's apparently married to a man named Spence (JAMES PUREFOY), various commandos raid the manor and want Alice's report. She has no idea what they're talking about, which also holds true for Spence, while the commandos cuff another man, Matt (ERIC MABIUS), who's also there.
After being informed of what's occurred, Alice and the others accompany the commandos - who include Rain (MICHELLE RODRIGUEZ), Kaplan (MARTIN CREWES), One (COLIN SALMON) and J.D. (PASQUALE ALEARDI) among others - down into the Hive where they must find and contain the virus before it infects the rest of the world.
Unbeknownst to them, however, the virus has an effect on the dead - it reanimates them. Thus, from that point on, and as Alice slowly begins to remember her role working for the Umbrella Corporation, she and the others race against the clock to accomplish their mission. While doing so, they must deal with the Red Queen's defensive measures as well as hundreds of undead zombies and other mutant creatures that repeatedly attack and can infect them with just one bite or scratch.