Vitamin D is a hormone with pleiotropic effects. It mainly regulates calcium and phosphate metabolism through interactions with FGF23 and its receptor klotho. In addition, it has been shown that Vitamin D also regulates the immune response and has protective effects from cardiovascular disease, cancer and infections. Most renal transplant recipients have overt Vitamin D deficiency, a condition that may be associated with a decline in graft function and other complications. After kidney transplantation, elevated levels of FGF23 may predict increased risks of death and allograft loss. Theoretically, an optimal Vitamin D supplementation might favor operational tolerance and protect transplant recipients from the triad cardiovascular disease-cancer-infection. However, more solid data are needed to confirm this and to set the optimal level of serum Vitamin D supplementation in order to attain the best clinical outcome.