Background　Anticoagulation is required for successful implementation of CPB. Particularly, appropriate dosing, monitoring, and maintenance of anticoagulation are essential to prevent devastating thrombosis of the CPB circulation or occlusion of the aorta, to minimize the stimulation of the coagulation system, and to improve the prognosis of the patients.　Objective　To review issues regarding heparin as an anticoagulant drug in extracorporeal circulation.　Content　Heparin is the most commonly used anti-coagulation drug because its action has many favoring features, including rapid onset, high capacitance, and readily reversibility. It activates fibrinolytic system to prevent thrombosis in CPB. But the variability of responses to heparin among individual patients pose demands for personalized regimens for its usage. To formulate a regimen, real-time monitoring of patients' coagulation system should be performed by measuring several critical parameters, including activated clotting time, levels of heparin, thromboelastography, etc. Protamine can be used to counteract with heparin. The risks of heparin-induced thrombocytopenia (HIT) should be taken into consideration before the operation. If patients have propensity to HIT or are resistant to heparin, heparin must be replaced with its substitutes.　Trend　Further investigations are demanded to improve the monitoring of the coagulation system in CPB and to develop better substitutes for heparin.