The paucity of active medical therapies for advanced prostate cancer underlies a critical need for clinical research in this area. Multiple new treatments are being evaluated, including therapies that target adrenal androgens, such as abiraterone; new chemotherapies, such as the oral platinum analog, satraplatin, and an epothilone analog, ixabepilone; combinations of chemotherapy with other agents, such as the VEGF inhibitor, bevacizumab, and calcitriol; as well as multiple immunotherapeutics, including sipuleucel-T, GVAX and ipilimumab. This review will highlight the promise of these new approaches and the challenges to their development.