Depot medroxyprogesterone acetate (DMPA) is the only injectable contraceptive available in the United States. After more than 20 years of regulatory review, the Food and Drug Administration approved DMPA for contraceptive use in 1992 after the publication of reassuring data about its possible association with breast cancer. It has been used by 30 million women in more than 90 countries. The recommended dosage, 150 mg intramuscularly every 3 months, has a contraceptive efficacy exceeding 99%. After a 150 mg dose, ovulation is inhibited for at least 14 weeks. Almost all users experience menstrual changes, typically episodes of unpredictable irregular spotting and bleeding, particularly during the first year of use. With continued use, spotting and bleeding decrease, and amenorrhea becomes common. Although ovulation suppression may rarely persist for as long as 18 months after the last injection, DMPA does not permanently affect fertility. Long-term DMPA use reduces menstrual blood loss, has been associated with a decreased incidence of candidal vulvovaginitis and pelvic inflammatory disease, and dramatically lowers the risk of endometrial cancer. Prolonged DMPA use may be associated with reversible reduction in bone density, probably related to suppression of endogenous production of estrogen. The most recently published data suggest that long-term use of DMPA induces moderate changes in lipid metabolism that are unfavorable in terms of risk of atherosclerosis. DMPA should be considered a highly effective, safe, convenient, and reversible contraceptive option for appropriately selected patients.