Although initially identified as a calcium homeostatic hormone, vitamin D is now known to have pleiotropic functions, dealing with both innate and adaptative immunity. Calcitriol mediates its biological effects by binding to the vitamin D receptor (VDR), which is expressed not only by intestine, bone and kidney but also on cell membranes of T lymphocytes, B lymphocytes, dendritic cells and macrophages. Vitamin D plays a role on the degree of liver damage in patients with chronic hepatitis C (CHC): low vitamin D levels have been associated with high hepatic necroinflammatory activity and progression of liver fibrosis. Vitamin D, in CHC patients, could also affect the response to antiviral therapy: in fact, recent studies have shown a relationship between low responsiveness to IFN-based therapy and low vitamin D serum levels. Further studies are required to better assess if vitamin D could work as a reliable noninvasive marker of liver fibrosis and whether vitamin D supplementation could be given to all CHC patients together with standard antiviral treatment, in order to improve the rate of sustained virological response (SVR).