Obesity results from a predominance of caloric intake over energy expenditure. Twin, adoption and family studies have demonstrated that, together with environmental conditions, various genetic factors play an important role in the pathogenesis of obesity. In recent years, it was possible to identify several defects in single genes responsible for obesity in rodents, some of which may also be involved in human obesity. Besides leptin as the most notable example, numerous other proteins and neuropeptides have been identified in recent years that participate in a complex network to regulate food intake and energy expenditure. The ongoing search for the important obesity genes should not only result in a better understanding of energy metabolism, but may also help in the development of new strategies for the treatment of obese patients.