Stress has been defined as an acute threat to the homeostasis of the organism. Themucosal lining of the gastrointestinal tract, a single layer of epithelial cells heldtogether by tight junctions, provides a barrier between the external environment andthe body’s internal milieu. Any mechanism that breaches the tight junction exposesthe body to foreign material be it protein, microorganisms or toxins. Stresses includephysiological (exercise), psychological, disease-related or drug-induced factors.Stress associated gastrointestinal disorders include functional dyspepsia irritablebowel syndrome (IBS), gastroesophageal reflux disease peptic ulcer disease, andinflammatory bowel disease (IBD). Some disease states disrupt gastrointestinal barrierfunction, e.g. infectious diarrhea, IBD, or celiac disease, whilst in others such aseczema it can be indirectly related to antigenic disruption of the barrier. Drugs, e.g.chemotherapy agents and nonsteroidal anti-inflammatory drugs, also disrupt barrierfunction. Malnutrition and nutritional deficiencies (zinc, folic acid, vitamin A) alsopredispose to mucosal damage. Assessment of gastrointestinal mucosal health hasproved problematic as invasive techniques, whilst useful, provide limited data and nofunctional assessment. Noninvasive tests particularly breath tests do provide functionalassessment and many can be used together as biomarkers to improve our abilityto define a stressed mucosa. Therapeutic options include pharmacotherapies,immunomodulation or immunotherapy.