Therapeutic options continue to expand for patients with multiple sclerosis (MS). MS is a potentially disabling, lifelong disease with a wide spectrum of clinical manifestations and tremendous interindividual variability of disease course. This chapter summarizes and integrates the evidence supporting the use of various agents such as natalizumab and glatiramer acetate, as well as other available but unapproved treatments, by outlining contemporary treatment strategies. It also focuses on early-course treatment decisions for established MS; the clinically isolated syndromes (CIS), management of aggressive MS, and future approaches are detailed. The therapies approved for relapsing forms of MS are discussed. The features of the available disease-modifying treatments (DMTs) are summarized and the pivotal trial data and clinically relevant interpretation of relapses and disability using the number needed-to-treat (NNT) are tabulated. Three Interferon-beta (IFNB) preparations are approved for relapsing MS: IFNbeta-1a, rebif, and IFN-beta-1b. Treatment intolerance or declaration of treatment failure should lead to switching therapy. Every MS patient should be encouraged to consider participation in a clinical trial, especially those patients who have breakthrough disease despite therapy, rapidly worsening MS, or progressive forms of the disease.