For a long time, reactive oxygen species (ROS) produced by the phagocyte NADPH oxidase (NOX2) complex have been considered harmful mediators of inflammation owing to their highly reactive nature. However, there are an increasing number of findings suggesting that ROS produced by the NOX2 complex also regulate T cell autoreactivity, thereby preventing development of a chronic inflammation, thus challenging existing dogma. ROS might not only be produced as a mechanism to eradicate invading pathogens, but rather as a means by which to fine-tune the inflammatory response, depending on when, where and at what amounts they are produced. In this review, I will describe the current findings highlighting ROS as regulators of autoimmune inflammation, focusing on autoimmune arthritis. 1. Olofsson P, et al Positional identification of ncf1 as an arthritis severity regulating gene in rats. Nat Gen 33:25-32, 2003 2. Hultqvist M, et al. Enhanced autoimmunity, arthritis, and encephalomyelitis in mice with a reduced oxidative burst due to a mutation in the Ncf1 gene. Proc Natl Acad Sci U S A 101:12646-51, 2004. 3. Gelderman KA, et al T cell surface redox levels determine T cell reactivity and arthritis susceptibility. Proc Natl Acad Sci U S A; 103, 12831-6. 2006. 4. Hultqvist M, et al A new arthritis therapy with oxidative burst inducers. PLoS Medicine; 3, 2006. 5. Gelderman, K. A., et al. 2007. Macrophages suppress T cell responses and arthritis development by producing Reactive Oxygen Species J Clin Invest 117:3020-3028. 6. Gelderman, K. A., et al 2007. Macrophages suppress T cell responses and arthritis development by producing Reactive Oxygen Species J Clin Invest 117:3020-3028. 7. Hultqvist, M., et al 2009. The protective role of ROS in autoimmune disease. Trends Immunol. 68:130-135 8. Hagenow, K., et al. 2009. Ncf1-associated reduced oxidative burst promotes IL-33R+ T cell mediated adjuvant-free arthritis in mice. J Immunol 183:874-881.