Almost all patients with metastatic prostate cancer will eventually develop hormone refractory disease. In general, these patients should be enrolled in a clinical trial designed to develop new therapies for the treatment of this disease. However, for a variety of reasons, some patients will not be candidates for these trials. In this setting, a secondary hormonal therapy is a viable option. Secondary hormonal therapy continues and extends the two basic approaches used in primary hormonal therapy: reduction in circulating androgens and competitive inhibition of androgen receptor binding. This article reviews the basic concepts of secondary hormonal therapy, including maintenance of testicular androgen suppression, the anti-androgen withdrawal syndrome, and the available agents. In addition, it reviews hormonal agents currently in development that act by other mechanisms to inhibit prostate cancer growth.