Prostate cancer is the most common cancer in men in the United States, and despite screening and early treatment, more than 27,000 men are predicted to die of the disease this year, almost all of whom will die of castrate-resistant, metastatic cancers that have progressed despite androgen deprivation therapy, also known as hormonal therapy. In recent years, an increased understanding of molecular mechanisms of prostate cancer progression and castration resistance has led to improved treatment strategies. This review focuses on emerging therapies for the treatment of castrate-resistant prostate cancer, with an emphasis on the importance of the drug targets as well as the state of current clinical trials, including those utilizing hormonal therapies, biological agents, and immunotherapy that are underway or have recently been completed.