Randomized, controlled trials of therapies for acute multiple sclerosis (MS) relapses have not been conducted in children. Clinical practice in the pediatric population is, therefore, based largely on adult practices. The treatment is based on steroids, intravenous immunoglobulin, and plasma exchange. This chapter discusses first-line disease modifying therapies using Interferon beta and glatiramer acetate, and second-line disease modifying therapies. It reviews immunomodulatory and cytotoxic agents that have been used in treatment-resistant cases, and the agents include natalizamab, CTX, mitoxantrone, rituximab. The oral agents described in the chapter are fingolimod, cladribine and IVIg. The approaches to frequently encountered psychosocial problems and symptoms in pediatric MS are: educational support, mobility, spasticity, affective disorders and depression and fatigue. Pediatric MS has been shown to carry a greater disease burden than adult MS, both in terms of annualized relapse rate and magnetic resonance imaging (MRI) parameters.