Over the past decade, biological immunotherapy has revolutionised the treatment of rheumatoid arthritis (RA). The most widely used of these therapies targets tumour necrosis factor-alpha (TNF-alpha). Approximately 20% of patients fail to respond to TNF-alpha antagonism, however, and a significant number of additional patients become refractory to anti-TNF-alpha therapy over time. Thus investigators have sought to target other pathogenic elements of RA using novel biological therapies. Abatacept is the first immunotherapy directed against the process of T-cell costimulation. Abatacept has shown clinical effectiveness in RA by improving disease activity, quality of life measures and radiographic progression of disease. In this article, we review the immunology of T-cell activation and costimulation, define the role of abatacept in this process, and discuss the clinical trials that led to the approval of abatacept as the latest biological therapy in RA in the USA and Canada. We also address the role of abatacept in the greater context of biological therapy for RA.