Multiple sclerosis (MS) is a complex autoimmune disease of the central nervous system. It is characterized by a proinflammatory and neurodegenerative process that results in neuroaxonal damage. Over the last two decades, a wide range of immunomodulatory and immunosuppressive treatments have been used for the management of MS. Several treatments have been developed or are under evaluation for reducing relapses, disease progression and long-term MS-related disability. Recently, a growing interest has emerged for therapeutics with very selective actions, particularly monoclonal antibodies, to target several biological pathways involved in MS. To date, only Natalizumab (Tysabri(®)) has been approved for the treatment of active MS forms. Its therapeutic mechanism is the blockade of the a4-integrin molecule of many leukocytes, which leads to a decrease of immune cells migration, in particular of lymphocytes, across the blood-brain barrier. Furthermore, other promising molecules are under study in clinical trials. In this review, we summarize and discuss the history, pharmacodynamics and safety of monoclonal antibodies that have been approved or are under evaluation for the selective treatment of MS.