Vitamin D is not really a vitamin but the precursor to the potent steroid hormone calcitriol (1,25-dihydroxyvitamin D3). Calcitriol, originally known for its regulation of calcium metabolism and bone homeostasis, has widespread extra-skeletal actions throughout the body including beneficial effects on the development and progression of cancer. The vitamin D receptor (VDR) is expressed in most tissues of the body. Most cancer data have been accumulated for colon, breast and prostate cancer but a benefit from vitamin D may be found in many cancers. Calcitriol regulates numerous extra-skeletal pathways that could play a role in determining cancer risk and prognosis including pathways involved in proliferation, apoptosis, differentiation, inflammation, invasion, angiogenesis and metastasis, and it therefore has the potential to affect cancer development and growth. Vitamin D status, which is determined by sunlight exposure, diet and supplements, might reduce the risk of developing cancer, and the appropriate regulation of cancer-relevant pathways by vitamin D might also have a place in the treatment of cancer. Multiple cell culture and animal models of cancer support a role for dietary vitamin D3 and calcitriol in retarding cancer development and progression; however, data from human clinical trials are thus far inconsistent. Randomized control trials in humans do not yet exist to conclusively support a beneficial role for vitamin D, however accumulating results from preclinical and some clinical studies strongly suggest that vitamin D deficiency increases the risk of developing cancer and that avoiding deficiency and adding vitamin D supplements might be an economical and safe way to reduce cancer incidence and improve cancer prognosis and outcome. If adequate vitamin D concentrations do reduce risk, ensuring that people receive sufficient vitamin D would be an easily available, economical and safe modality to reduce cancer incidence and mortality.