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Colon cancer is the secondary leading cause of cancer deaths in the US. Diet, both food and dietary supplements can play a key role in risk reductions. Clinicians should be resources for all patients for primary and tertiary risk reduction for colon cancer for disease prevention and health care cost containment.This symposium will present epidemiological, clinical and basic science evidence for nutritional chemoprevention of colorectal cancer. The food groups that will be reviewed for their include fruits, vegetables, fiber, garlic and fish. Nutraceutical supplements have been extensively reviewed as potential chemoprevention agents for colorectal cancer. Perhaps the strongest evidence has been linked to vitamin D intake. Suboptimal intake has been associated with heightened risk of colorectal cancer development and poor outcome. Vitamin D regulates many steps in oncogenesis and several of its analogues decrease intestinal tumorigenesis in animal models. Molecular, genetic, and clinical data in humans are scarce but they suggest that vitamin D is protective against colon cancer. Likewise, folate has been demonstrated to provide chemoprevention via epigenetic modulation of DNA methylation pathways. Accordingly, deficiency of folate may place individuals at higher risk for colorectal cancer. Other supplements that will be reviewed include calcium, selenium, folate, curcumin and vitamin B6. Finally, we will review the mechanisms for nutrient-genes interactions and epigenetics in cancer promotion and prevention.