Vitamin D itself is biologically inactive and has to be hydroxylated in the liver to 25-hydroxyvitamin D (25(OH)D) as the main circulating metabolite used for classification of the vitamin D status. 1,25 hydroxyvitamin D (1,25(OH)D) is produced through conversion by the enzyme 1-alpha-hydroxylase in the kidney. This vitamin D metabolite shows a higher affinity for the vitamin D receptor (VDR) compared to 25(OH)D. After binding and activation of the VDR three percent of the human genome will be regulated. Among the main role of vitamin D metabolites to regulate calcium and bone homeostasis, they also show non-skeletal effects with relevance in the development of several chronic diseases. In this context, vitamin D deficiency has been associated with an increased risk of cancer , cardiovascular, autoimmune, and infectious diseases, Based on these findings, a significantly reduced risk of mortality was shown in patients with oral vitamin D supplementation in randomized controlled studies.