Season One features 22 episodes that aired in the United States beginning September 13, 2005, and ending May 4, 2006. The first sixteen episodes aired on Tuesdays at 9:00 pm, after which the series was rescheduled to Thursdays. Sam and Dean Winchester lost their mother as children in a fire with supernatural elements. As a result, their father devoted his life to finding out what killed his wife so that he could seek revenge. He brought his sons on the road with him, training them to fight evil. Sam left this life as a "hunter" in order to attend college at Stanford University, while Dean stayed with their father. However, when their father goes missing while on a hunting trip, Dean asks Sam for help in locating him. Sam's girlfriend Jess is soon killed in the same supernatural manner that ended their mother's life, and Sam drops out of school in order to hunt the thing that killed her. They save innocent people along the way from supernatural creatures, and Sam starts developing psychic abilities. They eventually find their father, who reveals that the creature they seek is a yellow-eyed demon and that he plans to end its life with a mystical Colt revolver that can kill anything.
Season Two features 22 episodes that aired on Thursdays at 9:00 pm in the United States beginning September 28, 2006, and ending May 17, 2007. It follows Sam and Dean as they deal with their father's death and continue to hunt the demon with assistance from new allies Ellen, Jo, and Ash. Part of the demon's master plan is eventually revealed as he gathers Sam and others like him to fight to the death.
Season Three features 16 episodes that aired on Thursdays at 9:00 pm in the United States beginning October 4, 2007, and ending May 15, 2008. Originally 22 episodes were ordered for the third season, but production was halted on December 5, 2007, upon completion of the twelfth episode due to the 2007–2008 Writers Guild of America strike. The season number was shortened down to sixteen episodes, with four new episodes airing in April and May 2008. The plot focuses on trying to save Dean from his deal. Along the way, the brothers meet a demon named Ruby, who has an interest in Sam and claims to be able to help save Dean. Also, they meet Bela Talbot, an "acquirer" and seller of occult objects who is constantly a thorn in their side. The brothers eventually manage to track down the demon who holds Dean's contract—a being of great power named Lilith—and attempt to kill her.
Season Four features 22 episodes that aired on Thursdays at 9:00 pm in the United States beginning September 18, 2008, and ending May 14, 2009. It follows the brothers as they work with angels—Castiel, in particular—to stop Lilith's plan of breaking the 66 seals, which would let Lucifer walk free once again. Sam and Dean's relationship is also strained as Sam starts siding with Ruby over Dean, and gives into his demonic side more and more in order to become strong enough to defeat Lilith.
Season Five will feature 22 episodes and currently airs on Thursdays at 9:00 pm in the United States beginning September 10, 2009. Season Five is rumored to be the last season, due to Eric Kripke's statements over the years that he has planned for the show to run for five seasons. Despite this, Jared Padalecki and Jensen Ackles have contracts for a sixth season, if the CW chooses to once again pick up the show. The fifth season revolves around the fight to stop Lucifer and save the world from the Apocalypse.