This chapter examines scientific evidence for a dietary etiology of colon cancer and proposes dietary guidelines for the primary and secondary prevention of colon cancer. It also examines various diet-related initiators and promoters involved in colon carcinogenesis and the mechanism whereby dietary factors modulate colon carcinogenesis. The concept that dietary fat and certain fibers distinct from chemical contaminants of diet and from other environmental and genetic factors are important determinants of colon cancer risk is reinforced by biochemical epidemiologic studies in humans and laboratory animal studies. Cancer of the colon has been the subject of several epidemiologic reviews. In several populations consuming the diets high in total fat, dietary fiber acts as a protective factor for colon cancer risk. The biological plausibility of the nutritional factors in the etiology of colon cancer is reflected in a number of hypotheses for the mechanism of action.