This article discusses the merits and limits of nonsteroidal antiinflammatory drugs (NSAIDs), including cyclooxygenase (COX)-2 inhibitors, for colorectal cancer prevention. The suppressive effect of NSAIDs on colorectal tumors has been recognized since as early as 1981. The chemopreventive effect of NSAIDs on colorectal tumors in relationship to the inhibition of prostaglandin synthesis is reviewed first. Then, the results of a randomized double-blind clinical test that examined the regressive effect of a COX-2-specific inhibitor on adenoma of familial adenomatous polyposis (FAP) are presented. Other similar trials are also reviewed. The clinical guideline for the use of aspirin, NSAIDs, and COX-2 inhibitors for primary prevention of colorectal cancer that was prepared for the U. S Preventive Services Task Force is introduced. These results suggest that a higher dose of COX-2 inhibitors has a suppressive effect on adenoma of the colon and rectum, although a moderate clinical dose of COX-2 inhibitors does not induce clinically effective suppression of adenoma. In the future, NSAIDs may be tried in combination with other materials to prevent colorectal cancer.