The hemostatic system poses a major problem in extracorporeal membrane oxygenation (ECMO). The foreign surface in the extracorporeal circuit activates platelets and the clotting system. To avoid loss of platelets and activation of the clotting system, anticoagulation is necessary. In addition, in many patients on ECMO, preexisting clotting disorders are present. Therefore, bleeding and/or thrombosis are frequent complications in ECMO patients that require specific treatment and may even necessitate termination of ECMO. Most ECMO centers use heparin for anticoagulation and the activated clotting time (ACT) for monitoring. Reduction of problems with hemostasis may be obtained with less thrombogenic surfaces, new anticoagulants with a short half-life, platelet inhibitors, protease inhibitors, or selective anticoagulation in the extracorporeal circuit. While there will probably never be a complete nonthrombogenic surface available and all anticoagulants will have some risk of bleeding, improvement can be obtained by a combination of measures including better surfaces, more sophisticated anticoagulation regimens, and close laboratory monitoring.