Depot-medroxyprogesterone acetate (Depo-Provera(R)) is a highly effective, nondaily hormonal contraceptive option that has been available in the United States for a decade, and worldwide for 40 years. Benefits and risks of hormonal therapy are often under scrutiny; however, long-term clinical experience has established the safety of this long-acting contraceptive. This article reviews the contraceptive efficacy, potential noncontraceptive health benefits and long-term safety of with regard to risk of cardiovascular events, breast and gynecologic malignancy and osteopenia. Comparisons with other hormonal contraceptives are made as clinically appropriate. Common patient management issues, including effects on menstrual cycle, body weight and mood, are also addressed. Finally, this review provides recommendations for appropriate patient selection.