Prostate cancer is the second leading cause of cancer death in men. Long standing observations have found prostate cancer responsive to androgen suppression. The primary approach to androgen suppression for men with advanced disease (cancer that has spread outside the prostate gland) has been castration. However, medical or surgical castration eliminates only 90% to 95% of the daily testosterone production. The remainder is produced in the adrenal glands. In the 1980s Labrie hypothesized that counteracting adrenal androgens would further inhibit tumor growth and possibly improve symptoms and survival beyond the response achieved with monotherapy. In response to this hypothesis a number of anti-androgen agents were identified and used in combination with medical or surgical castration to obtain maximal androgen blockade (MAB). Despite multiple clinical trials and several meta-analyses the clinical efficacy and cost effectiveness of MAB compared with monotherapy has not been clearly established.