Obesity has a strong genetic component, which should be viewed as a predisposition only if certain environmental factors are present. Impaired regulation of both sides of the energy balance equation plays a role in the propensity to gain weight and develop obesity. Overeating may be induced in susceptible individuals by high dietary fat content, large portion sizes and low meal frequency. Increased metabolic efficiency in the form of a low resting metabolic rate has been identified in pre- and post-obese subjects, and the impact on total energy expenditure may be amplified by a low level of physical activity. A low thermic effect of food has been shown not to be a risk factor for weight gain, and post-obese subjects have a normal thermic effect of food. A genetically determined enhanced metabolic efficiency during overfeeding has been reported to contribute to fat gain. The heterogeneous nature of obesity indicates that different mechanisms, such as changes in the partitioning of fat (due to lipoprotein lipase activity, fat oxidative muscle enzymes) and carbohydrate, and an altered responsiveness of the sympathoadrenal system and thyroid hormones to a positive energy balance, seem to be involved.