Pediatric onset multiple sclerosis (MS) may be seen in 2-5% of patients with MS. It is characterized by high disease burden. As such, early treatment with preventative therapies should be considered. Although randomized controlled trials have not been conducted on therapies for pediatric MS, there is a growing body of literature suggesting safety of first-line agents approved for use in adult MS, including interferons and glatiramer acetate. The use of second-line therapies, such as natalizumab, cyclophosphamide, and mitoxantrone has been described in a small number of pediatric MS cases. These case series suggest benefit of these agents after limited follow-up. Little information on long-term effects of therapies such as cyclophosphamide, mitoxantrone, or natalizumab is available for this population, although concerns of increased risk for opportunistic infections (progressive multifocal leukoencephalopathy with natalizumab) and secondary hematologic cancers (with mitoxantrone) exist. Finally, although fatigue, motor, cognitive, and psychosocial difficulties are common in this population, no trials have been conducted on pharmacologic or non-pharmacologic interventions for the management of these problems. Therapies for spasticity, including baclofen (including the baclofen pump), diazepam, and botulinum toxin have been evaluated in children with cerebral palsy and may be used safely in children. Psychiatric intervention is often necessary for affective disorders. Interventions for fatigue have not been studied, although evidence in the adult MS literature suggests possible benefit of exercise and modafinil. This article provides a practical guide to the diagnosis and treatment of multiple sclerosis in pediatric patients.