Summary: Vitamin D regulates the function of many organs and systems, not only mineral and bone metabolism, it is also has plejotropic effects. Its deficiency may be associated with an increased risk for nearly all major human diseases. It is known that both 1-alpha-hydroxylase (CYP27B1) and vitamin D receptor (VDR) are present in almost every human tissue and that vitamin D may exert its actions via two general ways. First as the endocrine way with 1,25(OH)2D (calcitriol) as a hormone produced in kidneys, and second as paracrine, autocrine and intracrine ways, in which its precursor – 25(OH) D (calcidiol) is converted locally by CYP27B1 to 1,25(OH)2D in the target cell, which activates the VDR and downstream gene expression in the same or a neighboring, VDR-expressing cell. Moreover, a number of studies documented that this localized, tissue-specific conversion is a key determinant of many physiological processes and that it is substrate-dependent. In the review role of vitamin D in kidney disease is presented as well as its supplementation.