In childhood-onset multiple sclerosis (MS), the cerebrospinal fluid (CSF) profile is not fundamentally different from the adult-onset MS. Magnetic resonance imaging (MRI) is the best imaging technique to detect lesions suggestive of MS in children. The initial clinical course in most patients with childhood-onset MS is relapsing-remitting. In the UCSF cohort, the initial MS event was moderate or severe in 86% of children compared with 56% of adult-onset MS. In the UCSF pediatric-onset cohort, complete recovery was seen in 66%, which was similar to adults seen at the same center, questioning whether children have less irreversible neuronal injury during their first event or/and have a better ability to repair. MS is likely the result of a complex interplay between genes and environment. Potential prognostics factors associated with the assignment of disability milestones have been examined in several cohort studies from adult centers and one cohort from child neurology centers.