Hormonal therapy of breast cancer is the oldest treatment in advanced disease. Durable remissions can be obtained with a wide variety of hormonal manipulations. Oophorectomy was first used to reduce endogenous hormonal levels. Surgical procedures have been supplanted by drugs that reduce hormone secretion or block steroid hormone activity. Tamoxifen is the agent most widely used because of few side effects. Agonists can also be effective. Estrogens, androgens, and progestins have the same level of activity as surgical ablation or drug antagonists (20-40% overall response rate). More than 2,000 patients with advanced breast cancer worldwide have been treated with megestrol acetate in clinical trials. Reports of the trials show a response rate of 27%. In randomized trials, efficacy of megestrol acetate is comparable with tamoxifen and with other hormonal treatments. At the standard dose of 160 mg/day, the major side effect is weight gain. Studies are ongoing to evaluate if high doses of megestrol acetate may increase the response rate with acceptable toxicity.