BACKGROUND: Tight junctions (TJs) represent the major barrier within the paracellular pathway between intestinal epithelial cells. Disruption of TJs leads to intestinal hyperpermeability (the so-called "leaky gut") and is implicated in the pathogenesis of several acute and chronic pediatric disease entities that are likely to have their origin during infancy. AIM: This review provides an overview of evidence for the role of TJ breakdown in diseases such as systemic inflammatory response syndrome (SIRS), inflammatory bowel disease, type 1 diabetes, allergies, asthma, and autism. CONCLUSION: A better basic understanding of this structure might lead to prevention or treatment of these diseases using nutritional or other means.