Vagal sensory neurons mediate the vago-vagal reflex which, in turn, regulates a wide array of gastrointestinal functions including esophageal motility, gastric accommodation and pancreatic enzyme secretion. These neurons also transmit sensory information from the gut to the central nervous system, which then mediates the sensations of nausea, fullness and satiety. Recent research indicates that vagal afferent neurons process non-uniform properties and a significant degree of plasticity. These properties are important to ensure that vagally regulated gastrointestinal functions respond rapidly and appropriately to various intrinsic and extrinsic factors. Similar plastic changes in the vagus also occur in pathophysiological conditions, such as obesity and diabetes, resulting in abnormal gastrointestinal functions. A clear understanding of the mechanisms which mediate these events may provide novel therapeutic targets for the treatment of gastrointestinal disorders due to vago-vagal pathway malfunctions.