There is substantial evidence that rheumatoid arthritis is an autoimmune disease in which T cells are aberrantly activated. Existing therapies, including anti-tumor necrosis factor therapies, are successful for many patients, but the goal of lasting remission still frequently proves elusive. One novel therapeutic strategy is the blockade of T-cell co-stimulation to modulate T-cell activation. The first co-stimulation blocker to reach clinical trials is abatacept (CTLA4Ig). Initial abatacept trials have shown promise and further phase III trials are underway.