Mast cells are granulocytes derived from CD34+ pluripotent progenitor cells that demonstrate plasticity in their development, leaving the bone marrow and differentiating in the tissue where they ultimately reside. They are best known for their role in the allergic response, but also play a prominent immunoregulatory role in other processes, including immune tolerance, the innate immune response, angiogenesis, wound healing and tissue remodeling. Mast cells are found throughout the gastrointestinal tract; their metabolic products influence and regulate intestinal epithelial and endothelial function, gastrointestinal secretion, intestinal motility and absorption, and contribute to host defense. They also play an important role in the development of visceral hypersensitivity through bidirectional interaction with the enteric nervous system. Mast cells have been found to have an increasingly important role in the pathophysiology of a number of pediatric gastrointestinal diseases. This review summarizes the current understanding of the role that mast cells play in the development of pediatric gastrointestinal disorders, including eosinophilic esophagitis, functional dyspepsia, irritable bowel syndrome, celiac disease, inflammatory bowel disease, histologically negative appendicitis, Hirschsprung's disease, intestinal neuronal dysplasia, and food protein-induced enterocolitis syndrome.