There has been an explosion of knowledge of genetic variations among different populations and the influence of genetics on complex diseases such as rheumatoid arthritis (RA). Although class II major histocompatibility complex (MHC) alleles are important contributors, there are likely multiple other genes that modulate the disease phenotype. Genetic markers may allow prediction of response to particular treatments. Given the recent approval of tumor necrosis factors (TNF) inhibitors and the large number of biologic agents currently undergoing clinical trials, pharmacogenetic markers may prove to be clinically useful.