Abstract: The current view holds that chronic autoimmune diseases are driven by the continuous activation of autoreactive B and T lymphocytes. However, despite the use of potent immunosuppressants, the production of autoantibodies may persist and contribute to the autoimmune pathology. We recently demonstrated in autoimmune mice that both short‐lived plasmablasts and long‐lived plasma cells are involved in autoantibody production. While anti‐proliferative immunosuppressive therapy and monoclonal anti‐CD20 antibody deplete short‐lived plasmablasts, long‐lived plasma cells survive and continue to produce (auto)antibodies. Thus, strategies for targeting long‐lived plasma cells may provide potent new treatment modalities.