Macrophage migration inhibitory factor (MIF) was one of the first cytokines to be identified. In the early 1990s it was 'rediscovered' as a hormone that is secreted by the anterior pituitary gland and counter-regulates the anti-inflammatory effects of glucocorticoids. We now know that glucocorticoids stimulate the release of MIF from T cells and macrophages; this appears to be a physiological response to override the effects of glucocorticoids at the inflammatory site. However, this response can become pathological in acute respiratory distress syndrome (ARDS), in which high concentrations of MIF in the alveoli might contribute to ARDS pathogenesis. New insights into the structure and function of MIF, and the possibility of increasing the efficacy of glucocorticoids in the clinic by inhibiting MIF, are discussed in this review.