Multiple sclerosis (MS) is an inflammatory and degenerative disease leading to 
demyelination and axonal damage in the CNS. Autoimmunity plays a central role in 
MS pathogenesis. Per definition, monoclonal antibodies are recombinant 
biological compounds with a well defined target, thus carrying the promise of 
targeting pathogenic cells or molecules with high specificity, avoiding 
undesired off-target effects. Natalizumab was the first monoclonal antibody to 
be approved for the treatment of MS. Several other monoclonal antibodies are in 
development and have demonstrated promising efficacy in phase II studies. They 
can be categorized according to their mode of action into compounds targeting 
(i) leukocyte migration into the CNS (natalizumab); (ii) cytolytic antibodies 
(rituximab, ocrelizumab, ofatumumab, alemtuzumab); or (iii) antibodies and 
recombinant proteins targeting cytokines and chemokines and their receptors 
(daclizumab, ustekinumab, atacicept, tabalumab [Ly-2127399], secukinumab 
[AIN457]). In this review, we discuss the specific molecular targets, clinical 
efficacy and safety of these compounds and discuss criteria to anticipate the 
position of monoclonal antibodies in the diversifying armamentarium of MS 
therapy in the coming years.