PURPOSE OF REVIEW: Treatments targeting B cells are increasingly used for patients with multiple sclerosis (MS). We review the mechanisms of action, clinical effectiveness and safety of treatment, with emphasis on recently published studies. RECENT FINDINGS: Several monoclonal antibodies targeting the surface molecule CD20 on B cells are approved or being developed for treatment of MS. Overall, they seem comparable in terms of strongly suppressing radiological disease activity and relapse biology. Novel approaches include anti-CD19 antibody therapy and treatment with oral drugs targeting Bruton's tyrosine kinase (BTK). The main safety issue with persistent B cell depletion is an increased risk of infections - possibly including an increased risk of severe COVID-19. Vaccine responses are also blunted in patients treated with anti-CD20 antibodies. Lower doses or longer infusion intervals may be sufficient for control of disease activity. Whether this might also improve the safety of treatment and increase vaccination responses remains to be determined. SUMMARY: Available data support the widespread use of therapies targeting B cells in MS. Whether novel approaches targeting CD19 or BTK will have advantages compared to anti-CD20 antibody therapy remains to be established. Furthermore, trials investigating alternative dosing regimens for anti-CD20 antibody treatment are warranted.