To assist health professionals who counsel patients with overweight and obesity, a systematic review was undertaken to determine types of weight-loss interventions that contribute to successful outcomes and to define expected weight-loss outcomes from such interventions. A search was conducted for weight-loss-focused randomized clinical trials with >or=1-year follow-up. Eighty studies were identified and are included in the evidence table. The primary outcomes were a measure of weight loss at 6, 12, 24, 36, and 48 months. Eight types of weight-loss interventions-diet alone, diet and exercise, exercise alone, meal replacements, very-low-energy diets, weight-loss medications (orlistat and sibutramine), and advice alone-were identified. By using simple pooling across studies, subjects mean amount of weight loss at each time point for each intervention was determined. Efficacy outcomes were calculated by meta-analysis and provide support for the pooled data. Hedges' gu was combined across studies to obtain an average effect size (and confidence level). A mean weight loss of 5 to 8.5 kg (5% to 9%) was observed during the first 6 months from interventions involving a reduced-energy diet and/or weight-loss medications with weight plateaus at approximately 6 months. In studies extending to 48 months, a mean 3 to 6 kg (3% to 6%) of weight loss was maintained with none of the groups experiencing weight regain to baseline. In contrast, advice-only and exercise-alone groups experienced minimal weight loss at any time point. Weight-loss interventions utilizing a reduced-energy diet and exercise are associated with moderate weight loss at 6 months. Although there is some regain of weight, weight loss can be maintained. The addition of weight-loss medications somewhat enhances weight-loss maintenance.