Recognition of the link between coagulation activation and inflammation has led to the hypothesis that anticoagulants may be effective in the treatment of septic patients by altering the inflammatory response. However, only limited methodologies exist that can be used in human volunteers to mimic the physiologic alterations observed in critically ill patients. The human endotoxemia model represents a model of inflammation-induced tissue factor triggered coagulation activation. As it permits elucidation of a key player in this proinflammatory and procoagulant response, it serves as a useful tool to investigate novel therapeutics in a standardized setting. The aim of this review is to focus on coagulation interventions in the human endotoxemia model.