Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system (CNS). A growing body of evidence supports a role for vitamin D in MS aetiology. Vitamin D binding protein (DBP) is the major plasma carrier of vitamin D metabolites and genetic differences in DBP gene have been found to influence vitamin D levels. We review here evidence supporting a role of DBP in MS. Several recent studies show that DBP levels in the cerebrospinal fluid correlate with MS course, being lower during relapses and higher in the secondary progressive phase. Further studies are needed to elucidate the potential use of DBP as a biological marker of MS course, but may be of use given the current lack of diagnostic tools for the prediction of MS development and progression.