Rheumatoid arthritis (RA) is characterized by chronic inflammation leading to joint destruction. Regulatory T (T(REG)) cells are potent suppressors of autoimmunity, but are not capable of controlling every aspect of the inflammatory reaction. We have found that T(REG)-cell function is abnormal in patients with RA, and that a distinct population of T(REG) cells with potent suppressive properties is induced after therapy with inhibitors of tumor necrosis factor. In this Review, we discuss the mutual interactions between the opposing forces of T(REG) cells and inflammation in the context of RA. Therapeutic approaches that enhance T(REG)-cell function whilst controlling inflammation are likely to be the most effective strategies for restoring immune tolerance in patients with this disease.