A role for prostaglandins in maintaining mucosal integrity in the gastrointestinal tract is well documented. While traditionally the effects of prostaglandins on mucosal blood flow and epithelial function have been regarded as critical in the mechanism of action of these fatty acids, recent evidence that mucosal ulceration is almost invariably associated with mucosal inflammation has caused a reevaluation of the role of prostaglandins in mucosal defence. This review focuses on the ability of prostaglandins to exert anti‐inflammatory, and therefore anti‐ulcerogenic, effects in the gastrointestinal tract. These effects of prostaglandins are attributable to their ability to suppress the release of inflammatory mediators and reactive oxygen metabolites from a number of immunocytes, stromal cells and inflammatory cells. There is emerging evidence for cooperative interactions between prostaglandins and nitric oxide in maintaining mucosal integrity. Recent work on the inducible isoform of prostaglandin synthase as it pertains to mucosal defence is also reviewed.