Current evidence emphasises the immunomodulatory role of vitamin D, particularly through the enhancement of immune tolerance mechanisms. Vitamin D deficiency is an established risk factor for the development of autoimmune diseases, including multiple sclerosis. Vitamin D has a range of neuroprotective properties and remyelinating potential in multiple sclerosis patients. Reduced serum vitamin D levels are associated with progression of the disease, increased cognitive impairment, and fatigue. However, the therapeutic effect of vitamin D supplementation on clinical progression (incidence of relapses and disability progression) has not been confirmed. In contrast, some findings support a beneficial effect of vitamin D supplementation on radiological activity. Despite the above data, the use of vitamin D as an adjunct therapy to multiple sclerosis treatment is currently not a standardised recommendation. According to the Polish experts’ guidelines of endocrinological societies, patients with multiple sclerosis are considered a special risk group for vitamin D deficiency, which necessitates screening for vitamin D status based on the assessment of serum 25(OH)D concentration, with subsequent correction of deficiency under control of this parameter to achieve an optimal 25(OH)D concentration (>30–50 ng/mL). Prophylactic doses of cholecalciferol are 1,000–4,000 IU/day, depending on age. In contrast, the therapeutic dose of cholecalciferol is 4,000 IU/day, with 25(OH)D reassessment after 8–12 weeks of therapy. The presented principles of prophylactic and therapeutic treatment of vitamin D deficiency are associated with high efficacy and safety, and could potentially result in the enhancement of anti-inflammatory mechanisms and improved overall well-being in multiple sclerosis patients.