Obesity results from a prolonged small positive energy imbalance, and treatment needs to reverse this imbalance. Many different diets have been tried to treat obesity, and weight loss occurs with all of them. There is currently no evidence that supports the superiority of one macronutrient composition for diets over any other. The principal effect seems to be the degree of adherence to the prescribed calorie reduction. Obesity drugs have been developed that tap brain mechanisms for controlling feeding and the gastrointestinal tract and its peptides. Orlistat blocks intestinal lipase and produces modest weight loss. Sibutramine is a serotonin-norepinephrine reuptake inhibitor that has a warning on its label from the US Food and Drug Administration because of cardiovascular risk. Its marketing has been suspended in Europe. Several drug combinations are on the horizon for treatment of obesity.