Stress has been defined as an acute threat to the homeostasis of the organism. The mucosal lining of the gastrointestinal tract, a single layer of epithelial cells held together by tight junctions, provides a barrier between the external environment and the body's internal milieu. Any mechanism that breaches the tight junction exposes the body to foreign material be it protein, microorganisms or toxins. Stresses include physiological (exercise), psychological, disease-related or drug-induced factors. Stress associated gastrointestinal disorders include functional dyspepsia irritable bowel syndrome (IBS), gastroesophageal reflux disease peptic ulcer disease, and inflammatory bowel disease (IBD). Some disease states disrupt gastrointestinal barrier function, e.g. infectious diarrhea, IBD, or celiac disease, whilst in others such as eczema it can be indirectly related to antigenic disruption of the barrier. Drugs, e.g. chemotherapy agents and nonsteroidal anti-inflammatory drugs, also disrupt barrier function. Malnutrition and nutritional deficiencies (zinc, folic acid, vitamin A) also predispose to mucosal damage. Assessment of gastrointestinal mucosal health has proved problematic as invasive techniques, whilst useful, provide limited data and no functional assessment. Noninvasive tests particularly breath tests do provide functional assessment and many can be used together as biomarkers to improve our ability to define a stressed mucosa. Therapeutic options include pharmacotherapies, immunomodulation or immunotherapy.