Sepsis and septic shock represent a frequent cause of mortality in Intensive Care Units, despite of the progress in antibiotic therapy and in the hemodynamic and respiratory support. The most frequent cause of death is the Multi Organ Dysfunction Syndrome (MODS), which is the clinical manifestation of the irreversibile damage of the microvascular bed. During sepsis and septic shock both activation of coagulation /fibrinolysis and release of mediators of inflammation contribute to the pathogenesis of disseminated intravascular coagulation (DIC); in particular the formation of fibrin in the microvascular bed is the pathological substrate of the clinical development of MODS. The rationale for employing antithrombin (AT) concentrates in the treatment of DIC associated to sepsis is based on the consideration that AT plasma levels are always decreased in patients with sepsis or septic shock; furthermore, the degree of the decrease is directly proportional to the severity of the disease and the prognosis and low AT plasma activities correlate with high mortality. AT has a double function: anticoagulant and anti-inflammatory. The most important mechanism responsible of the anti-inflammatory properties of AT is the binding to the glycosaminoglycans of the endothelial cells and the consequent release of prostacyclin. During sepsis and septic shock, treatment with AT was able, especially in animal models but also in clinical studies, to decrease plasma levels of mediators of inflammation and in some case to preserve organ failure and to reduce mortality.