Although the effects of prostaglandins on gastrointestinal secretion, blood flow, and motility are quite well characterized, the mechanism underlying the cytoprotective actions of this group of lipid mediators has yet to be clearly established. It seems likely that the ability of NSAIDs to inhibit gastric prostaglandin synthesis is an important contributing factor to the pathogenesis of this disorder; however, it is still not clear why depletion of gastric prostaglandins predisposes the mucosa to injury. The study of prostaglandin receptors in the gastrointestinal tract is still in its infancy. As we learn more about the distribution of these receptors and develop specific agonists, it may become possible to develop prostaglandin analogues that are highly selective in enhancing mucosal defense but without the untoward effects frequently associated with analogues currently used clinically in the treatment of NSAID-induced gastropathy.