With its approval more than 15 years ago, subcutaneous etanercept (Enbrel^®) was the first biological disease-modifying antirheumatic drug (bDMARD) and the first tumour necrosis factor inhibitor to be approved for use in rheumatic diseases. Etanercept remains an important cost-effective treatment option in adult patients with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis or plaque psoriasis, and in paediatric patients with juvenile idiopathic arthritis or plaque psoriasis. In all of these populations, etanercept (with or without methotrexate) effectively reduced signs and symptoms, disease activity and disability, and improved health-related quality of life, with these benefits sustained during long-term treatment. The safety profile of etanercept during short- and long-term treatment was consistent with the approved product labelling, with adverse events being of a predictable and manageable nature. The introduction of etanercept and other bDMARDs as therapeutic options for patients with autoimmune rheumatic diseases and spondyloarthropathies revolutionized disease management and these agents continue to have a central role in treatment strategies. This article reviews the extensive clinical experience with etanercept in these patient populations.