The biggest question is where or not the Winchester Brothers have somehow allowed hell to escape from where it belongs and invade the world.
The series stars Jared Padelecki as Sam and Jensen Ackles as Dean as they try and put Lucifer back where he belongs before he starts the apocalypse.
"Supernatural" also stars Misha Collins as Castiel, Jim Beaver as Bobby, Kurt Fuller as Zachariah, Mark Pellegrino as Nick, Rachel Miner as Meg and Ron Benedict as Chuck.
The fifth season premiere, "Sympathy for the Devil," was written by Eric Kripke and directed by Robert Singer. It premieres Sept. 10 at 9 p.m. ET on The CW.
Enjoy these three clips from the premiere, courtesy of The CW.