The Raccoon City Police Department doesn't know what happened to the Special Tactics and Rescue Service (S.T.A.R.S.) team it sent out to investigate the Arclay Mountain area on the outskirts of the city, where a number of people have recently gone missing. The unit's helicopter seems to have crashed in the woods, and it hasn't received any contact from the squad since. The department decides to dispatch another S.T.A.R.S. unit, the Alpha team, to check things out. But something goes terribly wrong.

In Resident Evil for the Wii, players now have a wide range of control options, including the Wiimote and nunchuck in combination, which lets players shake the Wiimote to ready their weapons.