Many men who show evidence of a progression of prostate cancer by rising prostate-specific antigen (PSA) or other symptoms are treated with anti-androgens. Anti-androgen withdrawal represents the first line of treatment after failure of hormonal manipulation. Flutamide is an approved anti-androgen that has been incorporated in many of the combined androgen blockade studies. Bicalutamide is also a nonsteroidal anti-androgen that offers the advantages of reduced dosage amounts and reduction in side effects. Additionally, there are a variety of therapeutic agents that can suppress adrenal secretion of androgens. The most promising of these agents include aminoglutethamide, ketoconazole, and corticosteroids, with an expected response rate of 10% to 15%. Studies have shown that some patients may respond to an anti-estrogen such as tamoxifen. There are a variety of therapeutic treatment options available for patients with hormone refractory prostate cancer. However, quality-of-life issues are becoming increasingly important and should be incorporated into clinical trial endpoints.