The challenges in identifying genetic polymorphisms that influence the 
susceptibility to rheumatoid arthritis are the same as those faced in most 
complex diseases; genetic and phenotypic heterogeneity, an unknown number of 
loci presumed to have small genetic effects, non-genetic modifying effects that 
have yet to be fully characterised and a history of unconfirmed genetic 
associations. Despite the difficulties, the chronic nature of the disease, 
incomplete efficacy of existing therapies and resultant heavy healthcare burden 
for the developed world in managing patients with this condition, mean that an 
understanding of the genetic basis of disease susceptibility, severity and 
response to therapy is keenly sought. Many linkage and association studies have 
been carried out and in this article the results of linkage studies are 
summarised. Recently a number of convincing candidate genes have begun to emerge 
and an update has been provided for three of these: PTPN22, CTLA-4 and MIF.