Sipuleucel-T (Provenge) is the first therapeutic cancer vaccine approved by the US FDA. The approval heralds the long-awaited promise of improved patient survival with minimal toxicity by therapies designed to generate an active, specific anticancer immune response. The development of this first-in-class agent as well as other therapeutic vaccines in clinical evaluation has also led to a better understanding of relevant patient populations and end points for clinical trials. This article discusses the development and approval of sipuleucel-T in the context of other approved therapies for prostate cancer, as well as controversies and novel paradigms brought about by this new agent.