Over the past 20 y, higher-protein diets have been touted as a successful strategy to prevent or treat obesity through improvements in body weight management. These improvements are thought to be due, in part, to modulations in energy metabolism, appetite, and energy intake. Recent evidence also supports higher-protein diets for improvements in cardiometabolic risk factors. This article provides an overview of the literature that explores the mechanisms of action after acute protein consumption and the clinical health outcomes after consumption of long-term, higher-protein diets. Several meta-analyses of shorter-term, tightly controlled feeding studies showed greater weight loss, fat mass loss, and preservation of lean mass after higherprotein energy-restriction diets than after lower-protein energyrestriction diets. Reductions in triglycerides, blood pressure, and waist circumference were also reported. In addition, a review of the acute feeding trials confirms a modest satiety effect, including greater perceived fullness and elevated satiety hormones after higherprotein meals but does not support an effect on energy intake at the next eating occasion. Although shorter-term, tightly controlled feeding studies consistently identified benefits with increased protein consumption, longer-term studies produced limited and conflicting findings; nevertheless, a recent meta-analysis showed persistent benefits of a higher-protein weight-loss diet on body weight and fat mass. Dietary compliance appears to be the primary contributor to the discrepant findings because improvements in weight management were detected in those who adhered to the prescribed higher-protein regimen, whereas those who did not adhere to the diet had no marked improvements. Collectively, these data suggest that higher-protein diets that contain between 1.2 and 1.6 g protein $ kg 21 $ d 21 and potentially include meal-specific protein quantities of at least w25-30 g protein/meal provide improvements in appetite, body weight management, cardiometabolic risk factors, or all of these health outcomes; however, further strategies to increase dietary compliance with long-term dietary interventions are warranted. Am J Clin Nutr 2015;101(Suppl):1320S-9S.