Obesity is recognized as an inherited disease state, and attributes of modern civilization have enhanced its phenotypic penetrance greatly. Two thirds or more of obese persons suffer comorbidities,many of which are characteristic of (dys)metabolic syndrome of insulin resistance. Unfortunately patients with body mass index over 35 infrequently can achieve or maintain weight loss adequate to resolve these metabolic (and anatomic) issues by lifestyle or pharmacologic strategies and are served better by gastric bypass, in spite of its attendant risks, both surgical and nutritional. This article evaluates the metabolic consequences of obesity and highlights which of these are amenable to correction with weight reduction achieved by gastric bypass.