This chapter describes the coagulation pathway, the pharmacology of heparin, monitoring of anticoagulation status, problems associated with heparin usage, alternatives to heparin, the reversal of anticoagulation following termination of cardiopulmonary bypass (CPB) and the prevention and management of bleeding. Unfractionated heparin (UFH) remains the standard anticoagulant for CBP for several reasons. Activated clotting time (ACT) is a functional assay of heparin anticoagulation and is the most widely employed test. Thrombocytopenia can occur after CPB due to dilution of blood volume with the extracorporeal circuit volume and platelet consumption or sequestration. Platelet function impairment is considered to be the main hemostatic defect during CPB. The synthetic antifibrinolytic agents ε-aminocaparoic acid (EACA) and tranexamic acid (TA) bind to lysine binding sites in both plasminogen and plasmin and produce a structural change. This prevents the conversion of plasminogen to plasmin and also prevents the activation of plasmin.