The role of B lymphocytes in immunity to infections is not restricted to pathogen specific antibody production. These cells are endowed with many other capabilities (antigen presentation, modulation of the other immune cells functions, cytokine synthesis, formation of secondary lymphoid structures) that influence both the course and efficacy of the immune response. Similar to other autoimmune disorders, hyperactivity of B cells, as well as maturation and expansion of self-reactive B cell clones are characteristic also of rheumatoid arthritis. Many interplaying factors: intrinsic (gene polymorphism, defects in central and peripheral tolerance), and those generated in chronic inflamatory milieu (co-stimulatory signals, cytokines, growth factors, cell-to-cell contact, autoantigens release), are responsible for these B cell abnormalities. Recent reports have elucidated the critical role of B cells in self-sustaining chronic inflammatory processes and contributed to the rationale for the development of targeted therapies that functionally normalize or delete B lymphocytes.