A major goal in the area of cancer prevention and treatment is to make rational use of defined molecular targets in order to block carcinogenesis. Studies conducted in experimental animal models for many human cancers, including those of lung, skin, mammary gland, urinary bladder, colon, and pancreas, have demonstrated that carcinogenesis often may be inhibited by the administration of a highly diverse group of biologic and chemical agents. One very promising and well-studied target is cyclooxygenase (COX)-2. Interestingly, a number of cancers appear to overexpress the COX-2 enzyme, which may play several roles in carcinogenesis. Recent clinical studies have demonstrated the effect of COX-2 inhibitors in the treatment of familial adenomatous polyposis, a genetic disorder that increases the risk for developing colorectal cancer. Ongoing clinical trials with COX-2 inhibitors will increase our understanding and may give us profound insights into the general applicability of this new targeted approach for cancer control.