Several disease-modifying drugs (DMDs) are currently approved for the treatment of multiple sclerosis (MS). Recently, there has been increased identification and development of potential new treatments that may modulate the MS disease process, including oral therapies. Many of the newly approved MS therapies, as well as those in ongoing clinical trials, have the advantage of improved efficacy and/or being oral and more convenient, as compared to conventional injectable first-line MS therapies. However, many of these new and emerging MS treatments are known to be associated with serious adverse events, some of which may be potentially life threatening. Of additional concern, there is limited experience and long-term safety data for many of these drugs, and thus the true potential for complications associated with these agents remains ambiguous. With an anticipated explosion in the artillery of available MS therapies in the near future, neurologists will need to carefully weigh drug efficacy, convenience, safety, and tolerability when making therapeutic decisions. In this review, we describe the known mechanisms of action, efficacy, and side-effect profiles of new and emerging MS DMDs.