The gastrointestinal epithelium transports solutes and water between lumen and blood and at the same time forms a barrier between these compartments. This highly selective and regulated barrier permits ions, water, and nutrients to be absorbed, but normally restricts the passage of harmful molecules, bacteria, viruses and other pathogens. During inflammation, the intestinal barrier can be disrupted, indicated by a decrease in transcellular electrical resistance and an increase in paracellular permeability for tracers of different size. Such inflammatory processes are accompanied by increased oxidative stress, which in turn can impair the epithelial barrier. In this review, we discuss the role of inflammatory oxidative stress on barrier function with special attention on the epithelial tight junctions. Diseases discussed causing barrier changes include the inflammatory bowel diseases Crohn's disease, ulcerative colitis, and microscopic colitis, the autoimmune disorder celiac disease, and gastrointestinal infections. In addition, the main cytokines responsible for these effects and their role during oxidative stress and intestinal inflammation will be discussed, as well as therapeutic approaches and their mode of action.