Since Garland and Garland formulated the hypothesis that vitamin D may protect against colorectal cancer in 1980, various epidemiological approaches have been undertaken to evaluate this hypothesis. These approaches include studies based on regional solar UVB radiation, plasma- or serum-based studies, dietary studies, and those examining multiple factors that influence vitamin D status. Studies over the past several decades have tended to support that higher levels of vitamin D may decrease risk of colorectal cancer. An important implication is that current recommended dietary intakes such as 200-400 IU/d may be too low to exert appreciable benefits. To substantially reduce risk, higher levels of vitamin D associated with sunshine exposure or considerably higher intakes may be required. Recent studies also suggest a potential benefit of vitamin D on other digestive system cancers. One study suggested that a better vitamin D status at the time of diagnosis and treatment, as indicated by season of diagnosis, may improve survival from colorectal cancer. Darker-skinned individuals who tend to make less vitamin D may be at particularly high risk for digestive system cancer. The strong biological evidence for a protective role of vitamin D supports the epidemiological data. More study is needed to determine the optimal levels and intakes of this vitamin to optimally reduce colorectal cancer risk.