The liver plays a central role in the hemostatic system as it is the site of synthesis of the majority of proteins involved in hemostasis. Consequently, patients with advancing liver disease develop complex changes in their hemostatic system which include thrombocytopenia, low levels of coagulation factors, and low levels of fibrinolytic proteins. The net effect of these hemostatic changes is remarkably benign as patients develop simultaneous changes in pro- and antihemostatic pathways that neutralize each other. Although patients with liver disease may develop severe bleeding complications, the majority of severe bleeds are unrelated to hemostatic failure, but rather a consequence of portal hypertension or mechanical injury to blood vessels. Prohemostatic therapy is thus seldomly indicated to prevent or treat bleeding in patients with chronic liver diseases. Rather, prevention and treatment of bleeding in these patients focuses on reducing portal hypertension and addressing local vascular injury.