Rheumatoid arthritis (RA) is a multifactorial disease due to a combination of genetic and environmental factors. Identification of the genetic factors involved in the pathogenesis of RA should open up avenues for developing radical treatment strategies directed at the cause of the disease. The Association de Recherche sur la Polyarthrite (ARP) supports research in this field, in which our group has been involved since 1993. Thanks to this support, considerable progress has been made. Several combinations of susceptibility alleles of various genes are probably involved in the development of RA. Although HLA-DRB1 is the main RA gene, it accounts for only part of the familial risk for RA. HLA-DRB1 alleles are neither necessary nor sufficient to cause the development of RA in a given individual. Several genome scans conducted in populations from France, Japan, North America and UK have confirmed the role of the HLA region and suggested several other susceptibility loci. Association studies support a role for several genes, including TNFR2, PADI4, SLC22A4, RUNX1, and PTPN22. However, the imperfect matching of cases and controls requires that confirmation of these results be obtained. To confirm that a gene confers susceptibility to RA, the association must be replicated in several independent studies and, more importantly, evidence of genetic linkage must be obtained in family studies. The identification of genetic factors conferring susceptibility to RA will open up new avenues toward radical treatments for RA and may help to optimize the diagnostic, prognostic, and pharmacogenetic management of today's patients with RA.