The majority of randomized, controlled trials (RCTs) show only modest weight loss with exercise intervention alone, and slight increases in weight loss when exercise intervention is added to dietary restriction. In most RCTs, the energy deficit produced by the prescribed exercise is far smaller than that usually produced by dietary restriction. In prospective studies that prescribed high levels of exercise, enrolled individuals achieved substantially greater weight loss-comparable to that obtained after similar energy deficits were produced by caloric restriction. High levels of exercise might, however, be difficult for overweight or obese adults to achieve and sustain. RCTs examining exercise and its effect on weight-loss maintenance demonstrated mixed results; however, weight maintenance interventions were usually of limited duration and long-term adherence to exercise was problematic. Epidemiologic, cross-sectional, and prospective correlation studies suggest an essential role for physical activity in weight-loss maintenance, and post hoc analysis of prospective trials shows a clear dose-response relationship between physical activity and weight maintenance. This article reviews the role of physical activity in producing and maintaining weight loss. We focus on prospective, RCTs lasting at least 4 months; however, other prospective trials, meta-analyses and large systematic reviews are included. Limitations in the current body of literature are discussed.