Megestrol acetate was one of the first progestational agents to be evaluated for use in the hormonal therapy of advanced breast cancer. Since that time, megestrol acetate has become a standard for progestin antitumor research because of its progestational potency and excellent safety profile. As single-agent therapy, the average overall response rate to megestrol acetate therapy is 30%. This response rate is equivalent to that reported for tamoxifen, another hormonal agent widely used in treatment of breast cancer. Furthermore, although the side-effect profiles of these two agents are similar, the weight gain associated with megestrol acetate use may be beneficial in breast cancer patients who also have cancer cachexia. Because megestrol acetate and tamoxifen have been shown to be somewhat non-cross-resistant, megestrol acetate may prove useful as first-line treatment for disease that progresses during adjuvant tamoxifen therapy. Other focuses of research, including treatment of estrogen- and progestogen-receptor negative disease and moderation of weight loss for cancer cachexia, may offer hope to many cancer patients, even those with a currently unfavorable prognosis.