Multiple sclerosis (MS) is a demyelinating disease of the central nervous system and can have a wide range of presentations and disability levels. As a common neurological disease affecting those of working age, it has long been considered an adult disease. However, over the past 15 years, pediatric onset, defined as occurring in those ages 17 and younger, has become increasingly recognized and characterized. Pediatric-onset multiple sclerosis (POMS) represents only 3–5% of the MS population, making it a rare disorder of childhood. Rather than the typical physical disabilities associated with adult MS, pediatric patients often are neurologically intact but have “invisible” or hidden neuropsychiatric symptoms such as cognitive involvement and mood disorders, along with fatigue. It is also important to distinguish the initial onset of MS in a pediatric patient from the monophasic illness of acute disseminating encephalomyelitis (ADEM).