Progestational agents, such as megestrol acetate and medroxyprogesterone acetate, are effective hormonal treatments for metastatic breast cancer in postmenopausal women. Clinical trials of these agents have demonstrated that 30% to 60% of patients will experience objective tumor response, depending on pretreatment prognostic variables. Although optimal doses and schedules have not been fully defined, current studies are investigating the therapeutic effectiveness of high-dose progestins. Toxicity of these drugs is mild and generally limited to weight gain related to their anabolic activity. Progestins are active second-line agents for metastatic breast cancer in postmenopausal women. In selected patients, they appear to be equivalent to tamoxifen as first-line therapy for metastatic disease. As more patients are exposed to prolonged adjuvant tamoxifen therapy, the role of progestins as first-line hormonal therapy at the time of relapse is likely to expand.