These two guys go on road trips, and it's about what happens to them during that time. The book was, for the most part, a true life account of what happened to Jack Kerouac and one of his friends. He just changed their names. Kripke said once that he based Sam and Dean on those characters, which made me want to read the book even more.
If you pick it up, there's an edition with a blue cover, and it has a whole history of Jack and his friend Neal, and interesting facts about how long it took Jack to write the novel. (Well, I thought it was interesting, anyway.)