The single layer of epithelial cells that lines the GI tract must subserve the physiological imperative of selective permeability for nutrient and electrolyte uptake, while maintaining a barrier that restricts the ingress of toxins, pathogens and other undesirable substances into the body. The epithelium also simultaneously secretes fluid and electrolytes to facilitate the processes of digestion and absorption. Further, the epithelium also maintains a lifelong symbiotic relationship with a complex microbiota comprised of hundreds of commensal species that are normally harmless to the body. In the setting of various disease states, however, these homeostatic relationships are deranged, secondary to alterations in epithelial transport and barrier function, resulting, variously, in inflammatory infiltration, inappropriate immune responses to normally innocuous commensals, and diarrheal symptoms. An understanding of conditions such as the inflammatory bowel diseases (IBD) of Crohn’s disease and ulcerative colitis, or common GI infections such as salmonellosis, rests on a full description of epithelial properties. The transport capabilities of the epithelium evolve as cells mature along the crypt-villus (surface) axis, and also along the length of the intestinal tract. Although we do not yet have a full catalog of transporter expression in the gut in health and disease, I will review our state of knowledge in my presentation. It is also becoming evident that transporter expression, localization and/or function may be altered selectively by a range of GI pathogens and inflammatory cytokines. However, in contrast to the upregulation of chloride secretion that characterizes classical secretory diarrheal disorders such as cholera, fluid loss in IBD and in the setting of infection with invasive pathogens appears to result from a reduction in absorptive transport, leaving water in the lumen to be lost to the stool. This may reflect changes in epithelial proliferation that produce immaturity of the villus or surface cells. Paradoxically, these disorders appear also to be associated with a profound reduction in chloride secretion, which could have implications for host defense in the normally sterile crypts. It is also clear that diarrheal symptoms can be attributed to reductions in the barrier function of the epithelial layer, secondary to both genetic and inflammatory influences on proteins that make up, or regulate, intercellular tight junctions. Many of the derangements in epithelial properties that occur in the setting of infection or inflammation, moreover, can be reversed or prevented both in vitro and in vivo by the addition of probiotic microorganisms. Ultimately, an understanding of epithelial pathobiology in the gut may allow us to optimize these and other treatments for diarrheal illnesses.