Prior to 2010, the treatment options for castrate-resistant prostate cancer (CRPC) were limited. In the past 3 years, four new agents have been approved by the US Food and Drug Administration for use in CRPC. These four agents differ in their mechanisms of action and highlight the progress made in our understanding of CRPC, and more importantly, provide options with proven clinical benefit. This review examines the development, investigational evolution, adverse events, and future direction of: 1) the androgen receptor inhibitor, enzalutamide, 2) androgen biosynthesis inhibitor, abiraterone, 3) novel taxane chemotherapy, cabazitaxel, and 4) autologous immunotherapeutic agent, sipuleucel-T.