New molecular markers of coagulation and fibrinolysis activation have been developed and used to identify patient subgroups that frequently develop increased procoagulant turnover and, hence, disseminated intravascular coagulation and organ dysfunction. The idea of inhibiting the coagulation hyperactivation by the administration of antithrombin has led to experimental findings that pinpoint an anti-inflammatory action of antithrombin. Preliminary clinical trials of high-dose antithrombin administration in sepsis are promising. Point-of-care coagulation testing remains controversial since a variety of perioperative therapeutic regimens such as aprotinin administration obviously do not require ‘on-line’ coagulation monitoring.