The long-term effects on weight have only been studied for orlistat and sibutramine. The net effects of these drugs vary between 2-5% loss of weight after 1-2 years of treatment. However, the effects of orlistat and sibutramine on morbidity and mortality have not been studied extensively. In the past decade a huge amount of new knowledge has been gathered on the physiology of energy metabolism, satiety, gut-brain interactions, adipokines, adipogenesis, hypothalamic regulation etc. These studies have provided a multitude of new pharmacological targets for the treatment of obesity. Preclinical and clinical studies will have to prove the efficacy and safety of new drugs aimed at these new targets. The ultimate goal will be to reduce the increased morbidity and mortality, associated with obesity.