For years, proponents of some fad diets have claimed that higher amounts of protein facilitate weight loss. Only in recent years have studies begun to examine the effects of high protein diets on energy expenditure, subsequent energy intake and weight loss as compared to lower protein diets. In this study, we conducted a systematic review of randomized investigations on the effects of high protein diets on dietary thermogenesis, satiety, body weight and fat loss. There is convincing evidence that a higher protein intake increases thermogenesis and satiety compared to diets of lower protein content. The weight of evidence also suggests that high protein meals lead to a reduced subsequent energy intake. Some evidence suggests that diets higher in protein result in an increased weight loss and fat loss as compared to diets lower in protein, but findings have not been consistent. In dietary practice, it may be beneficial to partially replace refined carbohydrate with protein sources that are low in saturated fat. Although recent evidence supports potential benefit, rigorous longer-term studies are needed to investigate the effects of high protein diets on weight loss and weight maintenance.