The traditional approach to hemostatic disorders in the injured patient has focused on bleeding rather than a hypercoagulable state. This strategy continues despite growing evidence from studies of coagulation disorders in other patient groups highlighting loss of organ function secondary to inappropriate coagulation rather than hemorrhage. While traditional testing is useful in screening for low levels of coagulation factors or platelet dysfunction, only obvious bleeding or significant fibrinolysis is identified. Cellular interactions, in particular those of the vascular endothelium, are not taken into account by these assays. More than 20 years have passed since coagulation abnormalities were reported in patients with severe infection. Despite recognition of this association in sepsis, we are only beginning to understand how coagulation abnormalities develop in injury and to consider strategies to counter them. While hemorrhage may be successfully treated in patients following trauma, thrombosis in the microcirculation often contributes to end-organ damage with irreversible ischemic changes that may lead to death.