The sensory input to the CNS provides a basis for reflexes that control and coordinate gut function, integrates this with behavioral responses such as the regulation of food intake and also mediate sensations. Diverse sub-populations of afferents have been identified according to the morphologic appearance of their terminal distribution in mucosa, muscle and mesentery, their pathway to the CNS and their functional properties in detecting mechanical activity and the local chemical environment. Mechanosensitivity to distension shows remarkable plasticity and can be influenced by a wide range of chemical mediators released as a consequence of ischemia, injury and inflammation. Chemosensitivity is also a property of vagal mucosal afferents that sample the chemical milieu within the lamina propria for chemicals absorbed across the epithelium or released from enteroendocrine cells that are strategically positioned to "taste" luminal contents. A complex interplay between ion channels and receptors underlies gastrointestinal sensing mechanisms and determines appropriate responses during normal digestion and in pathophysiology.