Multiple sclerosis (MS) is associated with reduced bone mass and higher frequency of osteoporosis. Although high-dose short-term intravenous glucocorticoid regimens cause a decrease in bone formation, this effect is usually reversible and osteoporosis in MS patients may be independent of the short-term corticosteroid treatment. Clinical evidence suggests an important role of vitamin D as a modifiable risk factor in MS. Low circulating levels of vitamin D have been found in MS patients, especially during relapses, suggesting that vitamin D could be involved in the regulation of the clinical disease activity. Vitamin D mediates its function through a single vitamin D receptor (VDR). Polymorphisms of the VDR have major effects on vitamin D function and metabolism, and some VDR genotypes have been linked to osteoporosis and MS. Because the safety of high doses of vitamin D has not been established yet, vitamin D hasn't been used in enough doses to increase the serum level to a desired therapeutic target. Future clinical trials should determine the upper limit of vitamin D intake in order to achieve therapeutic benefit in MS patients.