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.