Pediatric multiple sclerosis (MS) represents a particular MS subgroup with unique diagnostic challenges and many unanswered questions. Due to the narrow window of environmental exposures and clinical disease expression, children with MS may represent a particularly important group to study to gain a better understanding of MS pathogenesis. Acute disseminated encephalomyelitis (ADEM) is more common in children than in adults, often making the differential diagnosis of MS, particularly a clinically isolated syndrome, quite difficult. Although both disorders represent acute inflammatory disorders of the central nervous system and have overlapping symptoms, ADEM is typically (not always) self-limiting. The presence of encephalopathy is much more characteristic of ADEM and may help in distinguishing between the two. Young children (under ten years old) with MS differ the most from adults. They have a lower frequency of oligoclonal bands in their cerebrospinal fluid and are less likely to have discrete lesions on MRI. Problems of cognitive dysfunction and psychosocial adjustment have particularly serious implications in both children and teenagers with MS. Increased awareness of these difficulties and interventions are needed. While clinical research on therapies to alter the disease course is limited, the available data fortunately suggests that disease-modifying therapy is well tolerated and likely to be effective. Ultimately, multinational research studies are necessary to advance our knowledge of the causes, symptoms, and treatment of pediatric MS and such collaborations are currently underway.