Several conventional methods of bariatric surgery can induce long-term remission of type 2 diabetes mellitus (T2DM); novel gastrointestinal surgical procedures are reported to have similar effects. These procedures also dramatically improve other metabolic conditions, including hyperlipidemia and hypertension, in both obese and nonobese patients. 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 resulting from surgical manipulation of the gastrointestinal tract. In this Review, we provide an overview of the clinical evidence that demonstrates 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.