Macrophage migration inhibitory factor (MIF) is a multipotent cytokine implicated in the pathogenesis of numerous inflammatory and autoimmune disorders. Since anti-cytokine therapy is considered to be a promising therapeutic strategy, selective targeting of MIF with either anti-MIF antibody or specific chemical MIF inhibitors might offer new therapeutic avenues for these disorders. Considering the unique relationship between MIF and glucocorticoids, therapeutic antagonism of MIF could also represent an effective approach for steroid-sparing therapies in patients with refractory autoimmune diseases.