There is increasing appreciation that multiple sclerosis (MS) can begin in childhood or adolescence, but pediatric MS continues to be a rare entity, with an estimated 2 to 5% of patients with MS experiencing their first clinical symptoms before age 16. A prompt diagnosis of pediatric MS is important to optimize overall management of both the physical and social impact of the disease. The widespread use of disease-modifying therapies (DMT) for MS in adults, as early as following an initial isolated episode, has led to the use of DMT in children and adolescents with MS. However, it is imperative to distinguish pediatric MS from other childhood CNS inflammatory demyelinating disorders such as acute disseminated encephalomyelitis. Although increasing evidence suggests a slower disease course in children with MS compared to adults, significant disability can still accumulate by early adulthood. Furthermore, associated neurocognitive deficits can impair both academic and psychosocial function at a critical juncture in a young person's life. This article reviews the clinical characteristics, neuroimaging, paraclinical findings, disease course, epidemiology, genetics, and pathophysiology of pediatric MS vis-à-vis adult MS. Further research of pediatric MS may advance our understanding of MS pathophysiology in general, as well as improve the long-term health care outcomes of children and adolescents diagnosed with MS. ©2007AAN Enterprises, Inc.