Monoclonal antibodies are a potent therapeutic approach for relapsing-remitting multiple sclerosis. This group of medications comprises diverse mechanisms of action resulting in both shared and unique adverse effects. Areas covered: The major trials and safety profiles of natalizumab, alemtuzumab, daclizumab, rituximab, and ocrelizumab are discussed. While each drug has a unique safety profile, one of the potential safety concerns for all of these drugs is infection, including for some progressive multifocal leukoencephalopathy. Other potential side effects and required monitoring for each drug are addressed. Expert opinion: The treatment of multiple sclerosis is a balance between efficacy and safety. As a group, these medications are highly effective, but not without notable safety concerns; therefore more research is needed to understand the place these medications hold in the overall treatment algorithm.