Epidemiologic studies have shown that colorectal carcinoma is a disease of Western civilization, most likely related to diet. Diet probably plays a multifactorial role, containing both protective and promoting factors for colorectal carcinoma development. Sorting through the complexities of diet has been a major challenge to epidemiologists. Diets rich in fat and calories seem to contribute to colorectal carcinoma formation, whereas diets rich in plant fiber seem to be protective. Animal studies implicate bile acids, cholesterol, and fatty acids as promoters of colorectal carcinoma, whereas fiber and calcium antagonize cancer promoters. Based on the recent recognition that mutations of specific colon cancer-associated genes correlate with progression of normal mucosa through adenomatous polyps to frank carcinoma, we now approach the question of dietary influences from a new prospective. How do dietary factors affect the mutagenic potential colonic luminal contents? As the links between molecular biology and epidemiology begin to form, new preventative strategies will be developed and tested that may prove to dramatically reduce the incidence of colon carcinoma.