RA is a chronic systemic inflammatory disease that primarily affects the small joints of the hands and feet, and results in a mean reduction in life expectancy of 3-10 years. RA is a multigene disorder with a substantial genetic component and a heritability estimate of 60%. Large-scale Genome-Wide Association Studies (GWAS) and meta-analyses have revealed common disease-associated variants in the population that may contribute cumulatively to RA pathogenesis. This review identifies the most significant genetic variants associated with RA susceptibility to date, with particular focus on the contribution of the HLA class II genes across different ethnic groups. Also discussed are the potential applications of pharmacogenomics to RA management by identifying polymorphisms associated with variation in treatment response or toxicity. The use of genetic variants to guide treatment strategy has the potential to not only reduce National Health Service costs, but also drastically improve patient experience and quality of life.