Cyclooxygenase2 (COX-2), an inducible prostaglandin G/H synthase, is overexpressed in several human cancers. Here, the potential utility of selective COX-2 inhibitors in the prevention and treatment of cancer is considered. The mechanisms by which COX-2 levels increase in cancers, key data that indicate a causal link between increased COX-2 activity and tumorigenesis, and possible mechanisms of action of COX-2 are discussed. In a proof-of-principle clinical trial, treatment with the selective COX-2 inhibitor celecoxib reduced the number of colorectal polyps in patients with familial adenomatous polyposis. Selective COX-2 inhibitors appear to be sufficiently safe to permit large-scale clinical testing and numerous clinical trials are currently under way to determine whether selective inhibitors of COX-2 are effective in the prevention and treatment of cancer.