Progestin therapy has become an established endocrine modality for the treatment of metastatic breast cancer, with medroxyprogesterone acetate and megestrol acetate being the most widely used agents. Both drugs display similar effectiveness as initial and secondary therapy for patients with advanced disease, with combined complete and partial response rates of approximately 30% to 40%. Uncontrolled trials have suggested that high doses of medroxyprogesterone may be more effective than lower doses, but randomized trials have yielded conflicting results. Clinical trials of megestrol acetate have demonstrated it to be an affective, well-tolerated oral progestin, and a recent randomized trial has suggested that higher megestrol acetate doses may be associated with not only improved response but also improved time to disease progression and survival. Further trials of high-dose megestrol acetate for both initial and secondary therapy are under way, and their results will provide valuable information concerning the role of such treatment.