Immunotherapy for castration-resistant prostate cancer has continued to be an area of active research over the last several years. The enthusiasm of this approach has been based on the assumption of better tolerability and that using the body’s own immune system may be more effective than either hormonal or chemotherapy. Sipuleucel-T, a dendritic cell–based vaccine, is the only approved agent in this class for the management of castrate-resistant prostate cancer. Although sipuleucel-T increases overall survival without any significant changes in progression-free survival, other forms of immunotherapy such as PSA-TRICOM, ipilimumab, and chimeric antigen receptor T cell therapy are in advanced stages of clinical development. Immune biomarkers are being developed to assess response to these treatments and also to understand how the immune system responds to these respective therapies. Combinations of immunotherapy with androgen deprivation, radiation therapy, and chemotherapy have also been explored with varying results. This review discusses the mechanisms, key preclinical and clinical data, and perspectives for immunotherapeutic agents in the treatment scheme for castrate-resistant prostate cancer.