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Biological drugs have brought new hope to patients with rheumatoid arthritis (RA) in whom previously existing treatments could not control inflammation, joint destruction, or the progression of disability. The five currently available TNF blockers are approved for treating RA patients, but they have different structures, morphology, pharmacokinetic properties, and activity. Randomised clinical trials (RCTs) have shown that they improve the signs and symptoms of both early and long-standing RA and other inflammatory arthritides, prevent radiographic progression, and improve the patients' health-related quality of life. However, they are more effective in combination with methotrexate (MTX) than alone. Combined treatment is generally well tolerated, and seems to be relatively safe in the short term, as confirmed by RCTs, long-term observational studies and in clinical practice. Patients who fail to respond or develop adverse effects - when treated with one anti-TNF agent can be successfully treated with a second TNF antagonist. However, in the case of primary failure, it is possible that biological agents with a different mechanism of action may be more successful. Tocilizumab alone or in combination with MTX is more effective than MTX monotherapy in reducing disease activity over 24 weeks. Abatacept is well tolerated and retains its efficacy over time, as does rituximab in non-responders to other anti-TNF drugs. Finally, although these drugs improve the quality of life of RA patients, they considerably increase direct medical costs., (Copyright © 2012 Elsevier B.V. All rights reserved.)