Large bowel cancer is one of the most common human malignancies in western countries, including North America. Several epidemiological studies have detected decreases in the risk of colorectal cancer in individuals who regularly use aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs). Clinical trials with NSAIDs in patients with familial adenomatous polyposis have demonstrated that treatment with NSAIDs causes regression of pre-existing adenomas. Preclinical efficacy studies using realistic laboratory animal models have provided scientifically sound evidence as to how NSAIDs act to retard, block, and reverse colonic carcinogenesis. Selective COX-2 inhibitors (celecoxib) as well as naturally occurring anti-inflammatory agents (curcumin) have proven to be effective chemopreventive agents against colonic carcinogenesis. There is growing optimism for the view that realization of preventive concepts in large bowel cancer will also serve as a model for preventing malignancies of the prostate, the breast, and many other types of cancer. There is increasing interest in the use of combinations of low doses of chemopreventive agents that differ in their modes of action in order to increase their efficacy and minimize toxicity. Preclinical studies conducted in our laboratory provide strong evidence that the administration of combinations of chemopreventive agents (NSAIDs, COX-2 inhibitors, DFMO, statins) at low dosages inhibit carcinogenesis more effectively and with less toxicity than when these agents are given alone.