In a small town in Colorado, Sam and Dean investigate a series of cattle mutilations, the beasts have been drained of their blood. They run across Jason, a hunter who specializes in vampires, but wonder why he's in town.
Sam and Dean reunite with their old friend Bobby. As they track down clues to John's whereabouts they find out that a buddy from John's Marine days has been murdered in a strange fashion.
Sam and Dean investigate a serial murder case and learn that since the 1960's similar murders have been repeated every 15 years. They meet Dr. Richard, the widower and Richard's young and beautiful second wife, Michelle. More attacks occur.
Lady luck? Not really. Sam and Dean stop by Las Vegas for a little fun and relaxation -- plus to try their hand at the tables. But bad luck soon befalls Dean, and there is some strange guy following him.
Drawn to a town lighting up with demonic signs, John meets Lily, a girl whose mother died in a fire years ago much like the one that killed Mary. John learns Lily has a fatal gift; if she touches someone they die.