Anticoagulation is an essential component of optimal extracorporeal membrane oxygenation (ECMO) management. Unfractionated heparin is still the anticoagulant of choice in most centers due to longstanding familiarity with the agent. Disadvantages include alterations in drug responses due to its capability to bind multiple heparin-binding proteins that compete with antithrombin and the potential for heparin-induced thrombocytopenia. In such cases, direct thrombin inhibitors are the treatment of choice but pose difficulties in monitoring due to the limited experience and target ranges for non-aPTT-guided management (aPTT: activated partial thromboplastin time). The current trend toward low-dose anticoagulation, especially for venovenous ECMO, is supported by data associating bleeding complications with mortality but not thromboembolic events, which include circuit thrombosis. However, only prospective data will provide appropriate answers to how to individualize anticoagulation, transfusions, and bleeding management which is currently only supported by expert opinion. Empiric therapy for ECMO patients based on laboratory coagulation alone should always be critically questioned. In summary, only collaboration and future studies of coagulation management during ECMO will help us to make this life-saving therapy that has become part of daily life of the intensivist even safer and more effective. Until then, a fundamental understanding of coagulation and bleeding management, as well as pearls and pitfalls of monitoring, is essential to optimize anticoagulation during ECMO. This article is freely available.