Multiple sclerosis (MS) is a heterogeneous demyelinating immune-mediated central nervous system disease, characterized by a wide variety of neurological signs and symptoms, which may be transient or permanent. In the acute phase, systemic corticosteroids and plasmapheresis are the first line treatments, while in the chronic phase immune-modulators (interferon, sphingosin-1-phosphate receptor modulators, monoclonal antibodies) are preferred. Vitamin D has antioxidant properties and has been suggested as a potential player affecting the development and progression of MS. Vitamin D deficiency increases the incidence of MS in clinical and Mendelian randomization studies. MS disease activity might be affected by vitamin D levels, with vitamin D deficiency being associated with rapid radiological progression. However, vitamin D treatment has no formal indication due to inconsistent clinical benefit. According to available clinical evidence and National Institute for Health and Care Excellence-NICE guidelines, vitamin D supplementation is not routinely recommended for the sole objective of MS treatment. However, as assuring normal serum levels of vitamin D is safe, might prevent MS and has potential clinical and radiological benefits, supplementation should be considered in all vitamin D deficient patients with MS.