Multiple sclerosis (MS), a leading cause of non-traumatic disability in young adults, is a chronic in flammatory demyelinating disease of the central nervous system (CNS) associated with aberrant autoimmune responses. It has long been thought that therapeutic development should be centered on immunomodulatory agents. However, none of the agents tested could prevent chronic progressive disease and disability. On the other hand, direct repair of injured myelin might represent an alternative strategy for treating MS. This may be achieved by either promoting the inherent repair mechanism of neurons or by recruiting cells derived from oligodendrocyte progenitor cells (OPCs), which are unfortunately silent in MS. The latter approach was recently demonstrated by Najm et al at Case Western Reserve University and Northwestern University. They demonstrated that miconazole and clobetasol, screened from a library of bioactive small molecules on mouse pluripotent epiblaststem cell-derived OPCs, promoted precocious myelination, significantly increased the number of new oligodendrocytes and enhanced remyelination. Strikingly, both small molecules reversed the disease severity in mouse models of MS.