Purpose of review: Not only the multiple sclerosis specialist but also the general neurologist and primary care practitioner are increasingly aware of possible adverse events (AEs) by treatment with alemtuzumab (over 47% risk of secondary autoimmune-mediated diseases). Vitamin D supplementation's effect (VDS) to reduce these autoimmune AEs is poorly performed in routine practice. This article seeks to justify why this simple, inexpensive, patient-friendly therapy should be seriously discussed. Recent findings: Patients who have developed autoimmunity also show a high basal level of IL-21, a cytokine which increases the growth of auto-reactive T-cells. For side effects such as thyroid dysfunction, autoimmune thrombocytopenia, autoimmune hemolytic anemia, autoimmune hepatitis, diabetes mellitus type 1, and alopecia areata/alopecia totalis, VDS may have an impact on the immunological mechanism, in particular lowering levels of IL-17 and IL-21. Summary: The potential role of vitamin D in influencing autoimmune diseases is evident. If a life-threatening side-effect can be prevented by high-dose VDS, it is ethical to initiate this add-on therapy despite contradictory results in studies on the effectiveness of VDS.