Although epithelial cells are continuously shed from the surface of the intestine, the intestinal epithelium maintains the integrity of the epithelial barrier. This is achieved through a highly dynamic process involving reorganization of tight junction and adherens junction proteins. This process both ejects the cell from the epithelial monolayer and plugs the gap left after the cell is shed. Inflammatory insults can trigger a disturbance of these barrier functions by increasing rates of cell shedding. Epithelial cell shedding and loss of barrier can be visualized by confocal laser endomicroscopy in humans. A simple grading system of confocal laser endomicroscopic images can stratify inflammatory bowel disease (IBD) patients in remission into those who will relapse over the subsequent six months and those who will not. Here, we review the mechanisms governing maintenance of these barrier functions and the implications of inflammation-induced barrier dysfunction in IBD.