The treatment of rheumatoid arthritis has changed dramatically in the last 10 years and in parallel the definition and expectations of patients and clinicians of the effects of disease-modifying anti-rheumatic agents has changed as well. Current expectations of efficacy now include improvement of signs and symptoms of disease activity as well as slowing, if not complete inhibition, of disease progression as measured by X-ray progression along with significant improvement in patient physical function. In addition, clinicians assess the safety profile of these agents more critically in an attempt to improve the risk:benefit profile. Drugs, such as methotrexate, sulfasalazine and leflunomide have provided patients with substantial relief of symptoms and improvement in terms of X-ray progression, but they have been hampered by the occurrence of significant adverse events along with the inability to maintain benefit for prolonged periods of time. With the increased understanding of the basic biological mechanisms of the disease process, there has been the introduction of four biological disease modifying therapies and other drugs into clinical practice, which have altered aspects of the risk:benefit ratio for patients with various rheumatic diseases.