In the last decade, with the implementation of new targeted drug therapy, the efficacy of the treatment of rheumatoid arthritis (RA) has increased enormously. However, a subset of patients still does not respond to any of the available treatments. At this moment, the chimerical anti-CD20 monoclonal antibody rituximab is one of the therapeutic options in RA patients who failed anti-TNFα therapy 1. After infusion it leads to a fast and almost complete depletion of CD20 positive B cells in the peripheral blood. In contrast to the peripheral blood compartment that has been studied quite extensively, only limited data exist on the effect of rituximab on other compartments of the immune system, like lymph nodes, bone marrow and synovial tissue. By studying the mode of action in the different inflammatory compartments, we may gain a more detailed understanding of the pathogenesis of RA and the mechanism of action of rituximab 2. In light of personalized medicine, this knowledge could lead to the identification of patients with a potentially improved clinical response, compared to for example patients who might need intensified dosing regimens or may better be treated with other drugs.