Excess bodyweight is the sixth most important risk factor contributing to the overall burden of disease worldwide. 1.1 billion adults and 10% of children are now classified as overweight or obese. Average life expectancy is already diminished; the main adverse consequences are cardiovascular disease, type 2 diabetes, and several cancers. The complex pathological processes reflect environmental and genetic interactions, and individuals from disadvantaged communities seem to have greater risks than more affluent individuals partly because of fetal and postnatal imprinting. Obesity, with its array of comorbidities, necessitates careful clinical assessment to identify underlying factors and to allow coherent management. The epidemic reflects progressive secular and age-related decreases in physical activity, together with substantial dietary changes with passive over-consumption of energy despite the neurobiological processes controlling food intake. Effective long-term weight loss depends on permanent changes in dietary quality, energy intake, and activity. Neither the medical management nor the societal preventive challenges are currently being met.