Macrophage migration inhibitory factor (MIF) is well established as a key cytokine in immuno-inflammatory diseases such as rheumatoid arthritis. Inflammation is now also recognized as having a crucial role in atherosclerosis, and recent evidence indicates that MIF could also be important in this disease. Here, we review the role of MIF in rheumatoid arthritis and atherosclerosis, discuss the ways in which MIF and its relationship with glucocorticoids could link these diseases, and consider the potential of MIF as a new therapeutic target for small-molecule and antibody-based anti-cytokine drugs.