Prostate cancer is an increasingly prevalent health problem among males, and the need for improved methods of treatment is great. In the 1940s estrogens were shown to be of benefit in prostate cancer, and their use continued for some 30 years, until the advent of LHRH agonists and similar drugs. At the time the mechanism of action of estrogens was thought to involve merely reduction in androgen levels, but new evidence, including expression of estrogen receptors by prostate epithelium and prostate cancer results showing a direct cytotoxic effect on prostate cancer, and preclinical data on inhibition of prostate cancer in intact female mice, suggests that estrogen exerts other effects on prostate cancer cells. Given that estrogens also decrease bone lysis caused by androgen suppression and may ameliorate cognitive side effects associated with low testosterone, estrogens show promise in treatment of androgen-independent prostate cancer. This review summarizes published reports of the effects on estrogens on prostate cancer in preclinical and clinical settings.