Vascular injury, whether surgical or traumatic, triggers a complex series of regulatory events. The understanding of these events, their interdependence, and their effect on hemostasis and thrombosis, is slowly being unraveled. The current understanding of these processes is reviewed in this paper. The application of this knowledge to the operating theatre has been slow and is severely limited by the lack of effective tools to monitor the coagulopathic status of individual patients. Hence, the initial treatment of patients with severe hemorrhage relies on improving the patient's physiological status and on basic surgical techniques. Should these efforts fail, then a number of topical hemostatic agents, selective inhibitors of fibrinolysis, and procoagulant molecules, such as recombinant factor VIIa, may be utilized. However, many of these agents have not yet been tested in clinical trials and studies are urgently needed to determine efficacy, safety, optimal dosage and time of administration.