For patients with relapsing-remitting multiple sclerosis (RRMS) uncontrolled on frontline treatments, there are now numerous options that improve disease control measured by annualized relapse rate (ARR). Only a subset of these therapies reverses functional deterioration measured by the Expanded Disability Status Scale (EDSS). Drugs that reduce ARR relative to first-generation therapies are labeled high-efficacy agents, but protection against neurodegeneration represents a more rigorous measure of benefit. High-efficacy agents such as fingolimod stabilize RRMS on the basis of ARR. Immunosuppressants such as alemtuzumab reverse functional decline. Like other potent agents used for induction in RRMS, the therapeutic window for alemtuzumab is relatively narrow, encouraging selective application for those informed of treatment goals and risks.