Shortly after multiple sclerosis (MS) was described by Charcot in 1872-1873, symptoms of MS were noted in children. At the time of these observations (late 19th century), the many inherited demyelinating diseases that manifest during childhood had not yet been recognized. Once the inherited demyelinating disorders became known, MS as a childhood disease was dismissed as a possible diagnosis. Only a half century later, with increased understanding of both inherited leukodystrophies as well as MS, was it acknowledged that children can develop MS. Our present challenges in the differential diagnoses of demyelinating disorders presenting in childhood are reflected in the history of pediatric MS.