An enhanced understanding of the immunopathology of rheumatoid arthritis (RA) has led to the development of novel therapies that target specific events occurring in the immune cascade that underlies the disease. In December 2005, abatacept became the first therapy to be approved by the US Food and Drug Administration for the treatment of adult patients with moderately to severely active RA who have exhibited an inadequate response to traditional disease-modifying antirheumatic drugs or tumor necrosis factor antagonists. This article summarizes the characteristics and clinical profile of abatacept. Abatacept is a fully human soluble recombinant fusion protein that acts by binding to CD80/CD86 on antigen-presenting cells and inhibiting interaction with CD28 on T cells, thus preventing one of the co-stimulatory signals needed for full T-cell activation. It is indicated for reducing signs and symptoms of the disorder, inducing a major clinical response, slowing the progression of structural damage, and improving physical function in this patient population. Data on abatacept compiled to date demonstrate significant efficacy, combined with a consistent safety profile and tolerability, in a wide range of patients with RA, including those with an inadequate response to methotrexate or to tumor necrosis factor antagonists.