Rheumatoid arthritis (RA) is a chronic, inflammatory condition of unknown aetiology that affects about 1% of the general population. Although the optimal care of RA patients requires various modalities, pharmacotherapy remains the cornerstone of treatment for established RA. The current therapeutic model encourages a step-up approach that safely incorporates several currently available classes of agents: non-steroidal anti-inflammatory drugs, selective cyclo-oxygenase-2 inhibitors, glucocorticoids, disease-modifying anti-rheumatic drugs, and biological agents (tumour necrosis factor-alpha inhibitors and interleukin-1 receptor antagonist). Non-steroidal anti-inflammatory drugs, selective cyclo-oxygenase-2 inhibitors and glucocorticoids, which offer a quick onset of symptom relief, are used mainly as adjunctive therapies. Disease-modifying anti-rheumatic drugs and biologicals have been successful in altering disease outcome and slowing radiographic progression. The indications, efficacy and safety of these agents in clinical trials and practice are reviewed in this chapter.