Vitamin D metabolites and analogs are known to play an important role in the development and prevention of bone mineral diseases and bony fractures. However, vitamin D is involved in a variety of cellular processes including innate immunity, cell proliferation, differentiation, and apoptosis. There have been a variety of studies investigating the role of vitamin D in the risk of developing cancer, particularly colorectal cancer. Many mechanistic studies show that the active vitamin D metabolite (1α,25-dihydroxyvitamin D3 or calcitriol) inhibits proliferation and promotes epithelial differentiation of human colon carcinoma cell lines that express vitamin D receptor via the regulation of a high number of genes. A key action underlining this effect is the multilevel inhibition of the Wnt/β-catenin signaling pathway, whose abnormal activation in colon epithelial cells initiates and promotes colorectal cancer. Calcitriol modulates gene expression and inhibits protumoral properties of patient-derived colon cancer-associated fibroblasts. High vitamin D receptor expression in tumor stromal fibroblasts is associated with longer survival of colorectal cancer patients. Moreover, many types of immune cells express vitamin D receptor and are regulated by calcitriol, which probably contributes to its action against colorectal cancer. Vitamin D also affects the gut microbiota that given the role attributed to the intestinal microbiota in colorectal cancer.