Whereas androgen deprivation and chemotherapy have become the cornerstone of therapy for advanced prostate cancer, novel therapies are being developed that may expand upon currently available treatments. The identification of antigens expressed by prostate tissue and/or prostate cancer that are recognized by T cells or antibodies creates opportunities to develop novel immunotherapeutic approaches including tumor vaccines. Proteins expressed in prostate cancer-including prostate-specific antigen, prostatic acid phosphatase, and prostate membrane antigen-have been used as immunologic targets for immunotherapy. Moreover, innovations in cancer genomics and proteomics also will aid in the identification of immunologic targets. Emerging trials have demonstrated that immunotherapy may generate not only immune responses in patients but also clinical responses. Future studies will be directed at capitalizing on these findings.