Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder that can lead to severe joint damage and is often associated with a high morbidity and disability. Disease-modifying anti-rheumatic drugs (DMARDs) are the mainstay of treatment in RA. DMARDs not only relieve the clinical signs and symptoms of RA but also inhibit the radiographic progression of disease and reduce the effects of chronic systemic inflammation. Since the introduction of biologic DMARDs in the late 1990s, the therapeutic range of options for the management of RA has significantly expanded. However, patients’ response to these agents is not uniform with considerable variability in both efficacy and toxicity. There are no reliable means of predicting an individual patient’s response to a given DMARD prior to initiation of therapy. In this chapter, the current published literature on the pharmacogenetics of traditional DMARDS and the newer biologic DMARDs in RA is highlighted. Pharmacogenetics may help individualize drug therapy in patients with RA by providing reliable biomarkers to predict medication toxicity and efficacy.