The range of available treatment options for patients with multiple sclerosis (MS) has expanded tremendously in recent years, adding further complexity to the therapeutic decision-making process. The first-generation therapies interferon beta and glatiramer acetate have been safely used for more than 20 years, but are only partially effective. Many of the newly approved MS therapies such as oral agents and monoclonal antibodies are selective immunosuppressants that appear to have improved efficacy and/or are more convenient, albeit in the absence of a long-term safety record. Although some are known to be associated with serious adverse effects, these treatments provide evidence-based therapeutic options for patients with suboptimal response or breakthrough disease. In this new scenario, non-selective immunosuppressive drugs and autologous hematopoietic stem cell transplantation are still present but likely play a more limited role than before. In this review, we briefly summarize the current, recent, and most imminent immunosuppressive therapies, and present an overall summary along with a discussion of their role in the current MS treatment scenario.