A protective effect of calcium on colorectal cancer, one of the most common malignancies in Western societies, has been supported primarily by results of in vitro animal studies. The present review summarizes the available epidemiological evidence for the association between calcium, vitamin D, and colorectal cancer. The overall results from over 20 published case-control and cohort studies suggest that calcium intake is not associated with a substantially lower risk of colorectal cancer. Findings from large prospective cohort studies, which should be least affected by methodological bias, have been notably consistent in finding weak and nonsignificant inverse associations. Whereas the relation between calcium and colon or colorectal cancer has been studied in numerous epidemiological studies, the role of vitamin D has only been addressed in a few of these investigations. The available results for vitamin D suggest that this micronutrient is inversely associated with risk but, given the scarcity of data, additional studies are needed to investigate this relation in more detail.