The introduction of low-fat, high-complex carbohydrate diets far the prevention and treatment of obesity was based on the causal link established between dietary fat and body fatness. Observational and mechanistic studies show that because fat possesses a lower satiating power than carbohydrate and protein, a diet rich in fat can increase energy intake. The propensity to gain weight is enhanced in susceptible persons, particularly sedentary people who have a genetic predisposition to obesity. Low-fat diets cause weight loss proportional to pretreatment body weight in a dose dependent manner; that is, weight loss is correlated positively to the reduction in dietary fat content. A reduction of 10% fat energy produces an average 5-kg weight loss in obese persons. As with traditional caloric counting diets, obese persons lose weight only if they adhere to the prescribed low-fat diet. Failure to achieve a weight loss and to maintain it may be attributed in part to lack of adherence to the diet. After a major weight loss, an ad libitum low-fat diet program appears to be superior to caloric counting in maintaining the weight loss 2 years later. Replacing some fat with protein instead of carbohydrate may increase the weight loss further. Moreover, fat substitutes may make it easier to prevent and treat obesity by making the diet palatable. More randomized, controlled, long-term dietary intervention studies are warranted to identify the optimal diet composition for the treatment of obesity.