Prostate cancer is the second leading cause of cancer death in men in the United States. According to the American Cancer Society an estimated 240,890 new cases of prostate cancer will be diagnosed in 2011 and 33,270 men will die from the disease. Immunotherapy is a form of biologic treatment that uses a therapeutic vaccine derived from cells in a patient’s own immune system to induce an antitumor response. Sipuleucel-T (Provenge), the first autologous cellular immunotherapy approved by the U. S. Food and Drug Administration, improves survival in men with asymptomatic or minimally symptomatic metastatic castration-resistant (hormone refractory) prostate cancer. This Clinical Brief discusses the epidemiology, natural history, and risk factors for prostate cancer, current diagnosis and treatment modalities, and the emergence of immunotherapy as a novel treatment to improve survival in men with advanced disease. Roger Muller, MD, FACEP, comments on managed care considerations. Safety information and full prescribing information for Sipuleucel-T are also provided.