Anti-CD20 monoclonal antibodies represent a particularly important class of drugs in the treatment of multiple sclerosis. This results from the discovery of the instrumental function of B cells in the initiation of multiple sclerosis autoimmunity, as well as their role in the protraction of the disease process. Ofatumumab is the first fully human anti-CD20 monoclonal antibody. Phase 2 and 3 trials demonstrated high efficacy of ofatumumab in a population of patients with the relapsingremitting and relapsing form of multiple sclerosis. Ofatumumab very efficiently decreased number of relapses. In comparison to placebo or the active comparator, teriflunomide, the annual relapse rate was reduced by more than 50%. Even more spectacular efficacy was demonstrated in the reduction of active magnetic resonance imaging lesions. Compared to teriflunomide, the number of gadolinium-enhancing lesions was reduced by more than 90%. In the pooled population from both phase 3 studies, ofatumumab also reduced the risk for disability progression. These data allow for the classification of ofatumumab in the group of high-efficacy treatment agents for multiple sclerosis. In a protracted disorder like multiple sclerosis, it is critically important to understand long-term efficacy and safety. To date, six-year data are available on ofatumumab treatment in relapsing-remitting multiple sclerosis. These results confirm the high efficacy of ofatumumab in long-term treatment in the population of relapsing-remitting multiple sclerosis patients.