A high correlation between national per capita disappearance of fat and national rates of colon cancer led to the hypothesis that consumption of fat, especially from animal sources, increases risk for colon cancer. Over the past two decades, this hypothesis has been tested in numerous case-control and cohort studies. In general, neither case-control nor cohort studies find that the total fat composition of the diet increases risk of colon cancer. Case-control studies frequently find that total energy consumption is related to a higher risk of colon cancer, but this result is difficult to interpret because physical activity appears to be protective whereas obesity increases risk. In contrast with the results for total fat, epidemiologic data regarding the role of specific fatty acids are sparse. Nonetheless, useful information regarding major fatty acids may be inferred from the numerous studies that have examined major source of various fats in relation to colon cancer. Intake of red meat or beef has been related to colon cancer risk in most case-control and cohort studies, whereas dietary fat from sources other than red meat, including dairy, poultry, and vegetable oils, does not increase risk of colon cancer. The apparent influence of red meat does not appear to be mediated through its total lipid content, suggesting that other factors such as heterocyclic amines formed during cooking may be critical. Mechanisms whereby fat or red meat may influence colon carcinogenesis are discussed, although none appear compelling.