Rheumatoid arthritis is a chronic autoimmune disease that often leads to functional disability and reduced quality of life. The pathogenesis of synovial inflammation that is associated with this disease is thought to result from T-cell activation. To become fully activated, T cells require an antigen-specific signal through the T-cell receptor and a second signal through a costimulatory receptor. Abatacept is the first drug in a new class of disease-modifying antirheumatic drugs (DMARDs) known as selective costimulation modulators. Costimulation modulators block the second signal and decrease T-cell activation. Abatacept has been approved by the United States Food and Drug Administration for reducing signs and symptoms, inducing major clinical response, slowing the progression of structural damage, and improving physical function in adults with moderate-to-severe active rheumatoid arthritis who have had an inadequate response to at least one other DMARD, such as methotrexate or tumor necrosis factor (TNF)-alpha inhibitors. Randomized controlled trials have shown that abatacept improves both clinical outcomes and health-related quality of life in patients who have had an inadequate response to other DMARDs. Abatacept has been shown to be well tolerated. In clinical trials, however, abatacept treatment was associated with a higher rate of infections compared with placebo. This finding was compounded when abatacept was used with TNF-alpha inhibitors; thus, this combination should be avoided. Abatacept appears to be a useful treatment option for patients with rheumatoid arthritis who have previously failed other DMARDs. However, additional clinical trials evaluating its long-term effect on patient safety and disease outcomes are needed.