Glucocorticoids (GCs) are widely used in the treatment of inflammatory diseases including rheumatoid arthritis (RA). Treatment with GC is associated with significant dose-dependent side-effects. The pro-inflammatory cytokine macrophage migration inhibitory factor (MIF) has emerged in recent years as a candidate factor which could regulate GC sensitivity. MIF is induced by GC, and is able to override anti-inflammatory actions of GCs. In this review, we summarize the pro-inflammatory actions of MIF with respect to RA, describe the interactions between MIF and GC and examine new evidence, which identifies MIF as a specific target for steroid sparing.