Androgen deprivation in patients with metastatic prostate cancer produces palliation of symptoms, reduction in PSA levels, and temporary regression of tumor in most patients. Following a brief period of disease regression that lasts an average of eighteen to twenty-four months, the disease becomes hormone refractory and progresses. Second line hormonal manipulation includes anti-androgen withdrawal, glucocorticoids, estrogens, aminogluthetimide, and ketoconazole. The response from these drugs is usually very short. Once these measures have been exhausted, the clinician is left with limited treatment options that include radionuclides and cytotoxic chemotherapy. It is the objective of this article to review the experience with chemotherapy in prostate cancer and then to discuss the role of radionuclide agents, emerging agents, and herbal therapies.