These last years were especially marked by the best understanding of the physiopathological mechanisms at the onset of rheumatoid arthritis (RA) and in the processes of joint inflammation and joint destruction. RA is more and more considered as a syndrome with at least two clinical entities with different phenotype and profiles: seronegative RA and seropositive RA. In RA with ACPA, it is the process of immunization, that is the immunological reaction against citrullinated peptides, that leads to the disease. The peptide citrullination is directly favored by environmental factors such as tobacco, infection to Porphyromonas gingivalis and alcohol. The immunization supposes a genetic predisposition including approximately 22 genetic factors including the molecules of the major histocompatibility complex (MHC) and PTPN22. Finally, joint damage result at the same time from an excess of destruction (RANK/RANKL, TNFalpha) and from a defect of bone reparation by the way Wnt/Frizzled. It is thanks to the best understanding of RA physiopathology that leads to development of targeted treatments and specially processing for this disease.