Although the development of disease-modifying antirheumatic drugs (DMARDs) and tumour necrosis factor antagonists has improved the clinical outcome of many patients with rheumatoid arthritis (RA), a substantial proportion of patients have an inadequate response. As T cells promote numerous disease pathways in RA, these cells are a logical target for anti-inflammatory therapy. Abatacept (CTLA-4Ig) is a soluble recombinant fusion protein which competes with CD28 for CD80 and CD86 binding and thereby can be used to selectively modulate T-cell activation. Several clinical trials have now confirmed the efficacy of this compound in the treatment of RA. This article discusses the mechanism of action and reviews the data from large clinical trials on the efficacy and safety of abatacept in RA.