There is convincing evidence that chemoprevention has the potential to be a major component of colorectal cancer control. Experimental, epidemiologic, and clinical studies provide evidence that nonsteroidal anti-inflammatory drugs (NSAIDs), particularly the selective cyclooxygenase (COX)-2 inhibitors, including celecoxib and several phytochemicals, act as anticancer agents. However, several of these chemopreventive agents induce side effects at effective high dose levels. Low doses of atorvastatin and aspirin, or atorvastatin and celecoxib, or piroxicam and difluoromethylornithine administered in combination are more effective in inhibiting chemically induced colon adenocarcinomas in male F 344 rats than are high doses of these agents given individually.