AbstractVitamin D is a conditionally required nutrient that can either be obtained from skin synthesis following UVB exposure from the diet. Once in the body, it is metabolized to produce the endocrine hormone, 1,25 dihydroxyvitamin D (1,25(OH)2D), that regulates gene expression in target tissues by interacting with a ligand-activated transcription factor, the vitamin D receptor (VDR). The first, and most responsive, vitamin D target tissue is the intestine. The classical intestinal role for vitamin D is the control of calcium metabolism through the regulation of intestinal calcium absorption. However, studies clearly show that other functions of the intestine are regulated by the molecular actions of 1,25(OH)2 D that are mediated through the VDR. This includes enhancing gut barrier function, regulation of intestinal stem cells, suppression of colon carcinogenesis, and inhibiting intestinal inflammation. While research demonstrates that there are both classical, calcium-regulating and non-calcium regulating roles for vitamin D in the intestine, the challenge facing biomedical researchers is how to translate these findings in ways that optimize human intestinal health.KeywordsVitamin DCalciumAbsorptionInflammationStem cellTight junctionCancerVDR