In this brief review, we focus on some of the proposed mechanisms of injury in peripheral visceral afferents (sensory) pathways and the enteric nervous system, including the interstitial cells of Cajal. Injury involving afferent neurons is discussed because of the relevance of these neurons to the pathophysiology of pain syndromes. The effect of various noxious stimuli on sensory and enteric neural function is examined. Finally, we discuss recent data on the role of autoimmune antibodies in neuronal injury in systemic diseases, such as diabetes mellitus and the Lambert-Eaton myasthenic syndrome. Neither central nervous system manifestations of peripheral nerve injury nor functional bowel disorders are addressed in this review. An improved understanding of the pathophysiology of peripheral neuronal dysfunction will probably result in new treatment strategies for a broad range of gastrointestinal disorders, including constipation, pseudo-obstruction, ileus, and inflammatory bowel disorders.