Recent advances in physiological understanding of obesity have provided a new perspective on its origins and potential treatments.This review is based on published literature in the fields of gut hormone physiology and the neuroendocrinology of obesity.The gut releases several hormones in response to changes in nutritional status. Changes in plasma concentration of these hormones are responded to by central nervous system circuits controlling appetite and energy expenditure. Modified gut hormone secretion is responsible, at least in part, for weight loss after certain forms of bariatric surgery.The extent to which modified gut hormone secretion is also responsible for remission of diabetes after bariatric surgery is contested, as severe calorie restriction alone can restore insulin secretion.Many gut hormone-based drugs are being developed for obesity.If suitable drugs receive marketing authorization, it will be important to discover whether their combined use, mimicking the hormonal milieu after bariatric surgery, can safely cause weight loss and metabolic benefits of similar magnitude to those resulting from bariatric surgery.