Selene (KATE BECKINSALE) is a vampire known as a death dealer. Her mission is to find Lycans, better known as werewolves, and kill them, since the two groups of monsters have been battling for centuries.
While proficient at her job, she's concerned that the Lycans can change from human to werewolf form at will, and that a group of them has some sort of peculiar interest in Michael Corvin (SCOTT SPEEDMAN), a human medical intern who's unaware of how his world is about to be turned upside down.
She reports this to her vampire leader, Kraven (SHANE BROLLY), who thinks she takes the warrior business too seriously. The two have never gotten along, especially since her mentor, the revered vampire leader Viktor (BILL NIGHY), went in a pre-ordained, centuries-long hibernation of sorts. And no one seems to believe her theory that the great Lycan leader, Lucian (MICHAEL SHEEN), is still alive.
Her reputation with her kind is further strained due to her interest in Michael who manages to save her after an attack by Lucian. After breaking all of the rules and resurrecting Viktor far too soon, Selene then sets out - with the aid of vampire technical advisor Kahn (ROBBIE GEE) - to figure out what the Lycans are up to and why Kraven doesn't want to heed her warnings.