Coagulation abnormalities, ranging from a simple fall in platelet count to full-blown disseminated intravascular coagulation, are a common occurrence in critically ill patients and have been associated with increased mortality. In sepsis, activation of the extrinsic coagulation pathway by tissue factor induces increased coagulation, and simultaneous depression of the inhibitory mechanisms of coagulation, and suppression of the fibrinolytic system results in a procoagulant state that may lead to the formation of microvascular thrombi disturbing organ microcirculation and promoting the development of organ dysfunction. Many inflammatory mediators are involved in the activation of coagulation, but many coagulation proteins are themselves actively involved in the inflammatory process. In this article, we explore the complex relationship between inflammation and coagulation and how improved understanding of this interaction has led to the development of new therapeutic agents for patients with severe sepsis.