- Jensen Ackles as Dean Winchester
- Jared Padalecki as Sam Winchester
- Jeffrey Dean Morgan as John Winchester
- Misha Collins as Castiel / Jimmy Novak
Jensen Ackles and Jared Padalecki as Dean and Sam Winchester, two brothers who travel the country looking for their missing father and battling evil spirits along the way. Sam Winchester is a college student bound for law school, determined to escape his family's past - unlike his older brother, Dean.
Ever since they were little their father has been consumed with an obsession to find the evil forces that murdered his beloved wife, and recruited his two young sons to help them. They have grown up as hunters of the supernatural.
Sam escaped this way of life after high school, and now has a happy life with his girlfriend, Jessica, and a promising future career. Dean, however, stayed behind with his father to join him in his "hunting".