Systemic inflammation is a potent prothrombotic stimulus. Inflammatory mechanisms upregulate procoagulant factors, downregulate natural anticoagulants and inhibit fibrinolytic activity. In addition to modulating plasma coagulation mechanisms, inflammatory mediators appear to increase platelet reactivity. In vivo, however, natural anticoagulants not only prevent thrombosis, but they also dampen inflammatory activity. Some insights into the evolution and linkages between inflammatory mechanisms and the coagulation/anticoagulation mechanisms have become evident from recent structural studies. This review will summarize the interactions between inflammation and coagulation.