When ER premiered on September 19, 1994, it focused on four up-and-comers – George Clooney, Anthony Edwards, Noah Wyle and Juliana Margulies – and became a hit based on stellar writing and cast chemistry. But when the series concluded fifteen (!) years later, everything looked very different. Clooney and Co. were long gone, and for the final season, John Stamos was the lead male actor. Seriously. John Stamos.