Rheumatoid arthritis (RA) is a heterogeneous autoimmune disorder of unknown cause with variable clinical expression. About 70% of patients are women. Genetic factors play an important role and likely account for about 60% of disease susceptibility and expression. The association with the HLA-DRB1 gene is the best understood, although several non-HLA loci have been linked to RA, including the 18q21 region of the TNFRSR11A gene, which encodes the receptor activator of nuclear factor kappaB, important in bone resorption in RA. Genetic factors are also important in the treatment of RA because the activity of enzymes relevant in the metabolism of drugs such as methotrexate and azathioprine, including methylenetetrahydrofolate reductase and thiopurine methyltransferase, are in part genetically determined.