Several dietary and other lifestyle factors have been implicated in the development of colorectal cancer. However, the precise nature and actual magnitude of the relationship between individual nutrient intakes and other lifestyle factors and colorectal cancer risk are not clear. A unifying hypothesis has recently been proposed that explains why obesity, physical inactivity, alcohol, and consumption of a typical Western diet increase colorectal cancer risk. This hypothesis suggests that these dietary and other lifestyle factors are associated with insulin resistance and hyperinsulinemia and that hyperinsulinemia, in turn, may stimulate growth of colorectal tumors. Two recently published large prospective epidemiologic studies indicate a significant increase in colorectal cancer risk in subjects with diabetes mellitus, thereby supporting this hypothesis.