Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that plays an important role in the pathogenesis of numerous inflammatory and autoimmune disorders. As such, it is an attractive therapeutic target for the treatment of these disorders. Several groups of possible MIF inhibitors have so far been identified, including anti-MIF antibodies, small chemical compounds and plant-derived inhibitors. This review presents current understanding of the effects of MIF neutralization in a number of experimental animal models of inflammatory and autoimmune diseases and discusses the potential problems in translating this kind of therapy into human subjects.