This chapter presents the literature review on disease-modifying therapies (DMT) for children with multiple sclerosis (MS). Four first-line DMTs have been approved for treatment of relapsing-remitting (RR) MS in the adult population. They include glatiramer acetate, interferon beta (IFNB)-1a IM, IFNB-1a SC, and IFNB-1b SC. Large phase III studies showed that chronic administration of recombinant IFNB reduced the number of relapses and slowed progression of physical disability in adult patients with RR MS. Abnormalities in liver function tests (LFTs) may be pronounced in younger children taking interferon. The glatiramer acetate is designed to mimic human myelin basic protein and is postulated to induce the myelin-specific response of suppressor T-lymphocytes and to inhibit specific effector T-lymphocytes. Breakthrough disease is a concern in the pediatric MS population. Proposed consensus criteria for breakthrough disease in adults include increase in relapse number, new or recurrent MRI lesions, and worsening of cognitive or motor disability.