Three major factors modulate body weight: metabolic factors, diet, and physical activity, each influenced by genetic traits. Despite recent advances in these areas, the prevalence of obesity in Westernized societies has increased. In contrast to monogenic animal models and rare human genetic syndromes, predisposition to common forms of obesity is probably influenced by numerous susceptibility genes, accounting for variations in energy requirements, fuel utilization, muscle metabolic characteristics, and taste preferences. Although recent increases in obesity prevalence cannot be explained by changes in the gene pool, previously "silent" genetic variants may now play important permissive roles in modern societies. Available data suggest that variations in resting energy expenditure, thermic effect of food, and fuel utilization exist but, by themselves, are unlikely to explain the onset of obesity. Regarding diet, the best available trend survey data indicate that fat and energy intake have fallen, in this and other Westernized countries. Diverging trends of decreasing energy intake and increasing body weight suggest that reduced physical activity may be the most important current factor explaining the rising prevalence of obesity. Subsistence in modern societies requires extreme adaptations in previously useful energy-conserving diet and exercise behaviors. Recognizing the difficulties in sustaining energy-restricted diets in the presence of fast foods and social feasts, the current trend toward increasing body weight is not likely to be reversed solely through recommendations for further reductions in energy intake. In all likelihood, activity levels will have to increase in response to an environment engineered to be more physically demanding.