Calcitonin gene-related peptide (CGRP), a 37 aminoacid-residue peptide, is a marker of afferent fibers in the upper gastrointestinal tract, being almost completely depleted following treatment with the selective neurotoxin capsaicin that targets these fibers via transient receptor potential vanilloid type-1 (TRPV-1). It is widely distributed in the peripheral nervous system of mammals where it is present as alpha isoform, while intrinsic neurons of the enteric nervous systems express predominantly CGRP-beta. Many gastrointestinal functions involve CGRP-containing afferent fibers of the enteric nervous system such as defense against irritants, intestinal nociception, modulation of gastrointestinal motility and secretion, and healing of gastric ulcers. The main effects on stomach homeostasis rely on local vasodilator actions during increased acid-back diffusion. In humans, release of CGRP through the activation of TRPV-1 has been shown to protect from gastric damage induced by several stimuli and to be involved in gastritis. In both dyspepsia and irritable bowel syndrome the repeated stimulation of TRPV-1 induced an improvement in epigastric pain of these patients. The TRPV-1/CGRP pathway might be a novel target for therapeutics in gastric mucosal injury and visceral sensitivity.