In contrast to other areas in rheumatology, the therapeutic armamentarium in systemic lupus erythematosus (SLE) has lagged behind due to a number of reasons. While SLE is the prototypical multi-system autoimmune disease, its low incidence and the heterogeneity in its clinical manifestations have made it difficult to study. Despite advances in the understanding and application of immunology, the emergence of new targets has not been successfully validated largely due to the difficult-to-use outcome measures. Among the many targets studied, co-stimulation blockade that prevents activation of T cells by antigen-presenting cells, poses an interesting concept that is plausible based on basic science, animal and early human studies. AREAS COVERED: The authors hereby review the development of abatacept in the treatment of SLE and possible future directions. EXPERT OPINION: Despite failure to achieve primary efficacy end points, the studies of abatacept in lupus provided tantalising evidence that co-stimulatory blockade is a feasible option worthy of further exploration.