The advancement of extracorporeal life support has introduced a new dimension to managing patients who do not respond to conventional treatment of severe cardiorespiratory failure. Extracorporeal membrane oxygenation (ECMO) is a specialized temporary life support that serves as a bridge to organ recovery or further treatment options. Owing to the interaction between the patient’s blood and the large artificial surface of the extracorporeal circuit, ECMO support triggers complex inflammatory and coagulation processes. This interaction can lead to disrupted microcirculation, endothelial injury, end-organ dysfunction, and hemostatic complications. As a result, systemic anticoagulation is essential to mitigate the risk of thromboembolic events and ECMO circuit failure. However, therapeutic anticoagulation carries a significant risk of clinically relevant hemorrhage, which may result in severe disability or death. Similarly, thromboembolic events may occur. To address these challenges, various anticoagulation and monitoring strategies are used, aiming to achieve a delicate balance between procoagulant and anticoagulant factors. This review highlights the latest studies of anticoagulation during ECMO support, emphasizing anticoagulation monitoring, associated costs, and potential future developments.