Alemtuzumab, a humanized monoclonal antibody that targets CD52, was recently approved in the EU and Canada for the treatment of patients with active relapsing-remitting multiple sclerosis. Alemtuzumab induces rapid depletion of circulating B- and T-lymphocytes followed by repopulation that leads to a distinctive lymphocyte profile, including an increased proportion of regulatory T-lymphocytes and memory B- and T-lymphocytes. In early open-label studies, alemtuzumab treatment reduced the number of clinical relapses and new MRI lesions in participants with secondary progressive MS. However, most participants had continued worsening of disability, which led to the evaluation of alemtuzumab in patients with early stages of disease in the Genzyme (MA, USA)-sponsored clinical development program in MS. In one Phase II and two Phase III trials, alemtuzumab reduced the number of clinical relapses versus the active comparator, subcutaneous IFN-β-1a, in treatment-naive and treatment-experienced participants with relapsing-remitting multiple sclerosis. Two of these trials showed reduction in risk of confirmed worsening of disability, and all showed reduction in cerebral atrophy. Safety issues include infusion reactions that are mitigated by pretreatment with corticosteroids in addition to symptomatic management with antihistamines; mild to moderate infections; and autoimmune adverse events. In this context, post-marketing risk mitigation strategies will be needed so that potential adverse events can be identified and managed early and effectively.