Etanercept is approved for the treatment of patients with moderate-to-severe active rheumatoid arthritis (RA), polyarticular juvenile RA, ankylosing spondylitis, psoriatic arthritis and plaque psoriasis. Randomized clinical trials have shown that it improves the signs and symptoms of early and long-standing RA and other inflammatory arthritides, prevents radiographic progression and improves the patients' health-related quality of life. It is more effective when combined with methotrexate than alone. It is generally well tolerated, and seems to be relatively safe in the short term, as confirmed by clinical trials, long-term observational studies and postmarketing surveillance over 12 years' use in clinical practice. It slightly increases the risk of serious infections. The incidence of malignancies during clinical trials and postmarketing surveillance is no different from that expected in the general population, except for the greater frequency of lymphoma. However, this is closely related to current RA activity and therefore suggests that it is not directly related to the drug. This article considers the published data in terms of clinical practice and changes in the progression of RA.