This review summarizes the existing literature regarding metabolic parameters and mood changes in women using depot medroxyprogesterone acetate (DMPA). MEDLINE and additional bibliographic sources were searched to identify English-language articles describing clinical trials and cross-sectional studies of DMPA published during the last 20 years. DMPA has little or no effect on glucose tolerance, but insulin levels may increase. An increase in low-density lipoprotein cholesterol and a decrease in high-density lipoprotein cholesterol have been observed in cross-sectional and longitudinal studies; however, there are no data to indicate whether the observed lipid alterations lead to adverse clinical events. There is some evidence suggesting decreased bone density in long-term DMPA users. Longitudinal data regarding bone density changes are needed to assess changes both during and after use. Most cross-sectional and longitudinal studies show increased mean weight or weight gain in DMPA users. Controlled studies of weight change that evaluate subgroups and effects of confounding variables are also needed to provide constructive advice to patients. Data regarding depression or mood changes in DMPA users are scanty and do not support a causal relationship between use of this contraceptive and affective disorders. For all of these parameters, case reports indicating adverse clinical outcomes are nearly absent from the literature despite widespread long-term international use of DMPA.