The diagnosis of rheumatoid arthritis has been hampered by the lack of a truly disease-specific serologic marker. Thus, despite its moderate specificity rheumatoid factor (RF) is still the only established marker antibody for RA and among the diagnostic criteria of the American College of Rheumatology the only serologic one. However, in recent years, several newly characterized autoantibodies have been described that may have the potential to become diagnostic indicators for RA. In particular, antibodies to citrullinated targets (anti-keratin or anti-filaggrin antibodies, respectively, antibodies to synthetic citrullinated peptides) appear to be highly specific for RA. Other potentially useful antibodies include anti-RA33 autoantibodies and antibodies to the stress protein BiP which seem to have higher specificity for RA than RF. Apart from being promising diagnostic markers these autoantibodies or the underlying cellular autoimmune reactions, respectively, may also play a role in the pathogenesis of RA.