The cytokine macrophage migration inhibitory factor (MIF) is a constitutive element of the host antimicrobial defenses and stress response that promotes proinflammatory function of the innate and acquired immune systems. MIF plays an important role in the pathogenesis of acute and chronic inflammatory or autoimmune disorders, such as sepsis, acute respiratory distress syndrome, asthma, rheumatoid arthritis, and inflammatory bowel diseases. Polymorphisms of the humanMIF gene (that is, guanine-to-cytosine transition at position -173 or CATT-tetranucleotide repeat at position -794) have been associated with increased susceptibility to or severity of juvenile idiopathic and adult rheumatoid arthritis, ulcerative colitis, atopy, or sarcoidosis. Whether theseMIF polymorphisms affect the susceptibility to and outcome of sepsis has not yet been examined. Analyses ofMIF genotypes in patients with sepsis may help to classify patients into risk categories and to identify those patients who may benefit from anti-MIF therapeutic strategies.