Pediatric-onset multiple sclerosis (MS) is a rare but increasingly recognized condition that both parallels and diverges from adult-onset MS. Exposure to key risk determinants for MS disease pathogenesis may occur during childhood. The diagnosis of pediatric MS can be challenging due to potential for atypical presentations and a broad differential diagnosis. MS disease-modifying therapies have not been rigorously studied in children and raise difficult questions on how to manage a chronic inflammatory neurologic disease in a population of patients with developing central nervous and immune systems.