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To discuss recent studies addressing the relationship between protease-activated receptor signaling, coagulation, and inflammation.This review article covers relevant original articles published until October 2003 dealing with animal models, clinical trial data, and in vitro experiments.Although activation of protease-activated receptors has been implicated in the proinflammatory effects of the coagulation cascade, current data provide evidence that protease-activated receptor signaling plays a more complex role in the regulation of inflammation and endothelial homeostasis. Sensitive assays for coagulation activation have provided clear evidence that targeting the coagulation pathway effectively reduces the coagulopathy in sepsis. However, the effect of these anticoagulant agents on sepsis-associated inflammation is less clear. Further insight into this question will require the development or use of additional biomarkers for assessing pharmacologic interference with coagulation-related cell-signaling pathways.