Bleeding is one of the major complications of surgery. Serious intraoperative and postoperative bleeding not only may be caused by a local problem in surgical hemostasis, such as a failed ligature, but also can be caused by a defect in the hemostatic system. Surgical hemostasis and an adequately functioning coagulation system are complementary: In some cases, a patient with a (minor) hemostatic defect may be operated on without any specific perioperative intervention in the coagulation system, whereas in other instances improvement of blood coagulation may be necessary before operation. In this chapter, current insights into the functioning of the coagulation system, and anticoagulant and pro-hemostatic interventions in this system, are discussed. Subsequently, conditions associated with an enhanced risk of perioperative bleeding (including the preoperative use of anticoagulant agents) and strategies to reduce perioperative blood loss are reviewed. Last, the pathogenesis and clinical management of disseminated intravascular coagulation (DIC) are discussed.