Recent years have broadened the spectrum of therapeutic strategies and specific 
agents for treatment of multiple sclerosis (MS). While immune-modulating drugs 
remain the first-line agents for MS predominantly due to their benign safety 
profile, our growing understanding of key processes in initiation and 
progression of MS has pioneered development of new agents with specific targets. 
One concept of these novel drugs is to hamper migration of immune cells towards 
the affected central nervous system (CNS). The first oral drug approved for MS 
therapy, fingolimod inhibits egress of lymphocytes from lymph nodes; the 
monoclonal antibody natalizumab prevents inflammatory CNS infiltration by 
blocking required adhesion molecules. The second concept is to deplete T cells 
and/or B cells from the peripheral circulation using highly specific monoclonal 
antibodies such as alemtuzumab (anti-CD52) or rituximab/ocrelizumab (anti-CD20). 
All of these novel, highly effective agents are a substantial improvement in our 
therapeutic armamentarium; however, they have in common to potentially lower the 
abundance of immune cells within the CNS, thereby collaterally affecting immune 
surveillance within this well-controlled compartment. In this review, we aim to 
critically evaluate the risk/benefit ratio of therapeutic strategies in 
treatment of MS with a specific focus on infectious neurological side effects.