Multiple systemic therapies have been used to treat patients with endometrial cancer. Although progestins have been the standard initial treatment for metastatic disease for the past 30 years, they are effective in only 20% of patients, and several large randomized trials have failed to demonstrate any benefit in the adjuvant setting. Alternative agents such as tamoxifen have shown modest activity. Few studies have investigated combinations of hormonally active drugs. Doxorubicin and cisplatin are the most active cytotoxic agents; a current randomized study is comparing the combination of these drugs with single-agent doxorubicin. Maximizing the effectiveness of established drugs, possibly with hematopoietic growth factors, and identifying alternative hormonal and cytotoxic agents with a sound scientific rationale will hopefully increase the effective treatment options for these patients.