Recently, chemotherapy for prostate cancer has been primarily reserved for the palliation of symptoms secondary to prostate cancer. Chemotherapy regimens and new approaches are being developed that offer new hope of response and improved survival to men with prostate cancer. This paper discusses pharmacological strategies that are under investigation: cytotoxic agents and biological or targeted therapies, including the microtubule inhibitors (taxane/taxoids, vinorelbine) alone and in novel combinations with other experimental agents such calcitriol, thalidomide or flavopiridol (cell-cycle inhibitor) and treatment with epothilone analogues; endothelin receptor antagonists; other novel strategies such as vaccine therapy (GVAX; Cell Genesys) and prostate-specific membrane antibodies; and bisphosphonates.