Etiology of rheumatoid arthritis remains unresolved. Initiating mechanisms include a genetic background of susceptibility, defined by HLA-DR4 and -DR1 antigens and also hormonal factors and infectious events. The synovitis is the hallmark of the disease. Lymphocytes infiltrating the synovial membrane are mainly memory CD4+ T cells associated to dominant clonotypes. The proliferation and cytokine production by synovial tissue T lymphocytes are weak. B cells produce locally auto-antibodies: rheumatoid factors, anti-keratin antibodies.... Type A and B synoviocytes constitute an hyperplastic synovial lining. They synthesize and release large amount of proteolytic enzymes and proinflammatory cytokines, largely participating to inflammation and tissue destruction. Understanding the pathogenesis of rheumatoid arthritis should offer novel approaches to treat rheumatoid arthritis patients.