If you are watching for the first time, these are the tentpole episodes:
Season 5 is the culmination of every thread planted since the pilot. The Winchester brothers find themselves as the predestined vessels for the Archangels Michael and Lucifer. The "destiny vs. free will" debate takes center stage as Sam and Dean fight to stop the Four Horsemen and prevent the end of the world. Supernatural Seasons 1-5
– The hunt focuses on Azazel (the "Yellow-Eyed Demon"). It explores Sam's emerging psychic abilities and culminates in the opening of a gate to Hell. Season 3: The Race Against Time
“We’re not going to let you go to Hell.” If you are watching for the first time,
When Supernatural premiered on The WB (later The CW) in 2005, it was a modest monster-of-the-week show about two brothers searching for their missing father. Few could have predicted that creator was secretly weaving a five-season master plan—a sprawling, mythological epic about fate, free will, family, and the biblical Apocalypse.
– After Dean sells his soul to resurrect Sam, the season focuses on the brothers' desperate attempts to break his crossroads contract before he is dragged to Hell. Season 4: The Introduction of Angels free will" debate takes center stage as Sam