The fundamental role of inflammatory immune processes in the pathology of multiple sclerosis (MS) provides the rationale for immunomodulatory therapies that attempt to shift the immune system from pro-inflammatory to anti-inflammatory pathways and induce regulatory mechanisms. Growing understanding of immune cellular and molecular mechanisms together with modern biotechnology engendered promising immunomodulatory treatment strategies, with novel mechanisms of actions and different levels of specificity. These include inhibitory molecules, monoclonal antibodies, cell therapies and agents that are administered orally or by infrequent infusions. Several of these treatments have demonstrated impressive efficacy in Phase II and III clinical trials by reducing disease activity and accumulation of disability. However, with the advent of potent therapies, rare but severe adverse effects, such as CNS infections and malignancies, have occurred. This article describes current and upcoming immunomodulatory strategies for MS therapy. The potential of immunomodulatory treatments to counteract the inflammatory characteristics of MS and support neuroprotective processes is discussed.