It's the year 2019, ten years after a vampire epidemic spread across the globe. Now with most everyone a blood-sucker -- many by choice to gain immortality -- those that didn't assimilate to that state are hunted down, captured, and then farmed for their precious commodity, human blood. The only problem is that with most everyone becoming vampires -- and then leading "normal" business and home lives like before -- humans are becoming an endangered species.
All of which means human blood is running out, a bad development since thirsty vampires soon turn into winged, scary-looking and decidedly less civilized "subsiders" that will attack regular vampires. As a result, one of the leading corporate suppliers of human blood, Bromley Marks, is looking for a solution and CEO Charles Bromley (SAM NEILL) wants chief hematologist Edward Dalton (ETHAN HAWKE) and his associate, Christopher Caruso (VINCE COLOSIMO), to come up with a synthetic blood replacement.
Edward wants to succeed, not for hopes of a promotion or even to quench his own thirst (he want to drink the real thing), but instead to save the human race, a desire he's held ever since his younger soldier brother, Frankie (MICHAEL DORMAN), bit and converted him over to the other side. Even Charles is conflicted as his daughter, Alison (ISABEL LUCAS), is still human and on the run somewhere.
Edward ends up running into some of her kind by accident, and Audrey Bennett (CLAUDIA KARVAN) senses that he isn't like the rest of the vampires. Accordingly, she introduces him to other humans, such as Jarvis Bayom (CHRISTOPHER KIRBY), but also Lionel "Elvis" Cormac (WILLEM DAFOE) whose heart hasn't beaten for years. A former vampire, he now works with Audrey in trying to save as many humans as possible while avoiding the armed vampire military that's always on the hunt for fresh human blood.
With only a short amount of time before that literally runs out and sends the vampire world into complete chaos, Edward does what he can to come up with a solution.