This paper provides an overview of the evidence on the current epidemic of obesity in the United States. The prevalence of overweight and obesity now exceeds 60% among US adults, and the rate is rapidly increasing among children and adolescents. Dismal medical, social, and economic consequences are already apparent and likely to worsen without multipronged intervention. Increased rates of hypertension, diabetes, and dyslipidemia, among other medical conditions, threaten to shorten the longevity of the American populace by as much as 5 years. The incidence of depression is increasing and experts suggest this is linked with the increased prevalence of obesity. The cost of obesity-related medical care has increased astronomically since 1987, in addition to lost productivity and income. Novel multidisciplinary, preventive, and therapeutic approaches, and social changes are needed that address the complex interplay of biologic, genetic, and social factors that have created the current obesity epidemic.