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Prostate cancer is the second leading cause of cancer death in men. Screening and advances in the treatment of localized disease may help reduce the burden of this disease. Unfortunately, despite progress in these areas, a significant number of men continue to present with advanced disease or to develop advanced disease at some time after treatment for their local disease. The treatment of advanced or metastatic prostate cancer is systemic therapy. The mainstay of systemic therapy for prostate cancer has been hormonal therapy for many years. Orchiectomy and estrogens were the initial hormonal therapies used. Over the past several years a number of agents have been shown to produce similar rates of disease control with improved tolerability profiles. The luteinizing hormone releasing hormone (LHRH) agonists are the most frequently used hormonal agents in prostate cancer. Antiandrogens have also been used as single agents, or in combination with LHRH agonists. Soon LHRH antagonists may come into clinical practice. When hormone therapy fails to control this disease, chemotherapy is the next line of treatment. Over the past several years, several newer chemotherapy agents have renewed enthusiasm for this avenue of treatment in prostate cancer. Novel agents utilizing a variety of recently identified mechanisms of action are likely to become clinically relevant in the treatment of prostate cancer over the next few years. This review seeks to address the major issues relating to the pharmacological treatment of advanced prostate cancer.