OBJECTIVE Prostate cancer continues to represent a major health problem. It represents the most common cancer in US men, with an estimated 186 320 new cases diagnosed in 2008. It is the second leading cause of cancer death in men in the United States. Despite several attempts, the median survival for men with metastatic castrate-resistant prostate cancer is 1-2 years, with improvements in survival seen primarily with docetaxel-based therapies. Treatment options are limited, and there is a clear need for therapies that improve outcome. The purpose of this article is to discuss recent developments in the field of metastatic hormone-refractory prostate cancer, including new cytotoxic agents, antiproliferative agents, immune-based therapies, circulating tumor markers and antiangiogenic agents. RESULTS During this last year, several promising approaches yielded disappointing results in the phase III setting (GVAX, satraplatin, DN-101); nonetheless, expectations for other agents (abiraterone, zibotentan, Provenge) still remain high. CONCLUSIONS These new agents will need to demonstrate survival benefit for approval. Circulating tumor cells have been shown to provide important prognostic information and are anticipated to be incorporated in future clinical decision-making.