I.I Mechnikov was the first who characterized phagocytosis as cellular defense mechanism. Infiltration of infectious process focus with phagocytes and subsequent activation of these cells is a fundamental defense reaction of the organism. However inflammation may be destructively dangerous if inflammatory response prolongates and/or generalization of the process leading to death of the host develops. The main trigger mechanisms in the pathogenesis of systemic inflammatory response and sepsis are release of bacterial endo- and exotoxins as well as hyperproduction of proinflammatory cytokines. Macrophage migration inhibitory factor (MIF) has exceptional multifunctionality and significant potential for activation of inflammatory system by various mechanisms acting as proinflammatory cytokine, hormone-contaregulator of immunosuppressive effect of corticosteroids and regulator of glucose metabolism. Data about the role of MIF as a crucially dangerous factor in pathogenesis of systemic inflammatory response obtained on experimental models of sepsis as well as about the efficacy of anti-MIF therapy were discussed, specific molecular mechanisms were analyzed. Prognostic value of high blood concentration of MIF during septic complications in clinic situations was assessed. In general, existing data on key role of MIF in sepsis pathogenesis show that MIF is one of the most promising targets for development of new strategies of immunotherapy for this life-threatening pathology.