Multiple sclerosis (MS) onset in childhood occurs in a small proportion of individuals with the disease, although the precise incidence of pediatric MS is unknown. It may be difficult to distinguish the initial attack of pediatric MS from acute disseminated encephalomyelitis, particularly in very young children. Environmental and genetic factors that appear to increase the risk of pediatric MS include prior infection with Epstein-Barr virus, exposure to cigarette smoke, and HLA-DRB1*15 haplotype. Children may have more posterior fossa involvement at onset and a higher relapse rate than adults with MS. Although time to disability may be longer than in adults, pediatric MS is associated with an earlier age of disability. Off-label use of standard disease-modifying therapies for adult MS is common, although data regarding the efficacy and safety for these medications are limited.