Prostate cancer is the leading cause of cancer in men in the United States, with 234,460 men expected to be diagnosed as having the disease in 2006 (33% of cancers in men), and the third leading cause of cancer deaths in men, with 27,350 men expected to die of the disease (9% of cancer deaths). Through early detection and improved local therapies, including surgery or radiation therapy, a large number of men will be cured, but unfortunately, a significant number of men will still experience relapse of disease and require continued surveillance and ongoing therapy. This article discusses approaches to treatment of men who have recurrent disease, including active surveillance, androgen ablation therapy, secondary hormone therapy, chemotherapy, bisphosphonates, radiation therapy, and future directions.