Several conventional methods of bariatric surgery and some novel gastrointestinal surgical procedures induce long-term remission of type 2 diabetes mellitus (T2DM). In addition, these procedures dramatically improve other metabolic conditions, including hyperlipidemia and hypertension, in patients with and without obesity. Several studies have provided evidence that these metabolic effects are not simply the results of drastic weight loss and decreased caloric intake but might be attributable in part to endocrine changes that result from surgical manipulation of the gastrointestinal tract. In this Review, we provide an overview of the clinical evidence that demonstrate the effects of such interventions-termed metabolic surgery-on T2DM and discuss the implications for future research. In light of the evidence presented here, we speculate that the gastrointestinal tract might have a role in the pathophysiology of T2DM and obesity.