Supernatural is the story of Dean and Sam Winchester. They are brothers. They are hunters of the supernatural. The series has a main story arc that also features a "monster of the week". Very similar to The X-Files.
The first season has the Winchester boys searching for their father, who is searching for yellowed eyed demon that killed their mother. Eventually, the demon finds them.
The second season has Sam and Dean contining the quest to kill the yellowed eyed demon, who reveals that Sam has demon blood in him and is special.
Season 3 deals with Dean trying to get out of his contract with Lillith, a powerful demon. Sam realizes the demon blood has given him special powers.
Season 4 has the brothers working with Castial, an angel, to try and stop Lillith from breaking the 66 seals and releasing Satan from Hell. Sam along battles his demonic side as it starts to take over.
Season 5 will wrap up the main story arc of stopping the Apocalypse.
Much of season 4 and 5 focus on the main story arc of the devil, along with his legion of demons, battling angles for control of the Earth. Each group has their own selfish reasons of why the want to win.
I cant speak highly enough about this show. It has become one of my favorites on television. Part drama, part horror, part western, and a bit of comedy makes it great. I find it fascinating how the show has involved from a monster show into one about the end of days, yet the outline for this battle was in the first three season all along. It all an amazing set up to something more profound.
The main characters are strong and are individuals. At times you love Dean and Sam while other you want to beat them. And that's usually at different times for each. Jensen Ackles and Jared Padalecki do an outstanding job.
If you never watched the series, give it a chance. You wont be disappointed.
The official Supernatural website can be found HERE