The gastrointestinal tract represents the largest interface between the human body and the external environment. It must continuously monitor and discriminate between nutrients that need to be assimilated and harmful substances that need to be expelled. The different cells of the gut epithelium are therefore equipped with a subtle chemosensory system that communicates the sensory information to several effector systems involved in the regulation of appetite, immune responses, and gastrointestinal motility. Disturbances or adaptations in the communication of this sensory information may contribute to the development or maintenance of disease. This is a new emerging research field in which perception of taste can be considered as a novel key player participating in the regulation of gut function. Specific diets or agonists that target these chemosensory signaling pathways may be considered as new therapeutic targets to tune adequate physiological processes in the gut in health and disease.