Since 2004, five drugs with new mechanisms of action have been approved by the US Food and Drug Administration for the treatment of relapsing forms of multiple sclerosis (MS). The expanded armamentarium of treatment options offers new opportunities for improved disease control and increased tolerability of medications, and also presents new safety concerns and monitoring requirements with which physicians must familiarize themselves. We review each of the newly approved agents-natalizumab, fingolimod, teriflunomide, dimethyl fumarate, and alemtuzumab-with regard to their mechanism of action, clinical trial data, safety and tolerability concerns, and monitoring requirements. We also review available data for promising agents that are currently in late-phase clinical trials, including daclizumab, ocrelizumab, and ofatumumab.