The development of incretin hormones and incretin analogues for the therapy of diabetes highlights the importance of the gastrointestinal tract in the maintenance of glucose tolerance. The review focuses on recent information on the role of incretins and their breakdown products on insulin secretion, gastric emptying, and satiety. The importance of gastric emptying and its absorptive potential as well as of dietary composition on gastric emptying and glucose tolerance is highlighted. The concept of a portal glucose sensor in humans has been the subject of some controversy but has been recently revisited. The gastrointestinal tract plays an important part in glucose tolerance. In this review we have examined how factors altering gastric emptying, insulin secretion in response to meal ingestion, and gastric emptying contribute to the maintenance and deterioration of glucose tolerance.