Obesity is a risk factor for many diseases including cardio-vascular disease, type 2 diabetes, and certain forms of cancer, among others. Obesity results from a chronic imbalance between calorie intake and energy expenditure. Genetic factors obviously play an important role in weight gain, but only in certain environments. The principal cause of the obesity epidemic is not clear: is obesity due to excessive food intake, a dynamic reduction in energy expenditure, or an association of these two factors? However, most obese subjects gain weight because of an inaptitude to adjust energy expenditure in response to excessive food intake. In this article, we review briefly the respective role of genes and environment in the development of obesity, then describe metabolic risk factors involved. Longitudinal studies conducted in Pima Indians have demonstrated that a relative decrease in basal metabolism, weak lipid oxidation in the fasting state, reduced spontaneous physical activity, and lower sympathetic nervous system activity are risk factors for obesity. Unlike our growing knowledge of food intake regulation, little is known about the control of energy expenditure. New discoveries should provide information on obesity susceptibility genes and increase the chances of developing new anti-obesity treatments.