Prevention of human diseases has become a major focus of biomedical investigators around the world. Our current screening and treatment regimens for colorectal cancer are not effective, as indicated by the fact that this disease is the second leading cause of death from cancer in the United States. Recently published reports indicate that continuous use of aspirin reduces the relative risk of colorectal cancer by about 50%. Other work demonstrates that NSAIDs cause regression of adenomas in patients with familial adenomatous polyposis and prevent the development of colon tumors in carcinogen-treated animals. This review is a summary of the literature and includes an analysis of recent reports indicating the potential molecular basis for the chemoprotective effects of NSAIDs.