B-cells play an important role not only in cellular but also in humoral immunity through differentiation into plasma cells and antibody production. B-cell depletion may, theoretically, change the course of systemic rheumatic diseases (SRD) in which self-reactive antibodies are part of the pathogenic pathway. In Rheumatology, anti-B-cell antibody Rituximab is currently licensed for the treatment of rheumatoid arthritis, however there is growing evidence of its potential use in other SRD. The authors present a case series of eight patients in which Rituximab was used off-label including overlap syndrome Rhupus, systemic lupus erythematosus and Wegener's granulomatosis. In the end, a brief literature review about this subject is performed.