The role of cytokines in the pathogenesis of rheumatoid arthritis (RA) has been a fertile area of research in the last two decades. The strongest supporting evidence for the importance of cytokines in RA is provided by the efficacy of treatment with specific antagonists of tumor necrosis factor (TNF) and interleukin-1 (IL-1). Despite the specific nature of such therapies, however, many patients remain either unresponsive or incompletely responsive. This has led to the growing consensus that other cytokines must also be important in this disease (1). There is little doubt that the search for important etiologic factors in RA is far from over, in terms of both understanding the disease and creating improved treatments. We review herein the evidence for the role of the cytokine macrophage migration inhibitory factor (MIF) in inflammation. We also review the unique relationship between MIF and glucocorticoids, which suggests that therapy with an MIF antagonist may provide specific “steroid-sparing” effects in the treatment of inflammatory diseases. A substantial body of evidence now implicates MIF in the pathogenesis of symptoms and disease progression in RA, validating its potential as a therapeutic target in this disease.