In cardiac surgery involving cardiopulmonary bypass (CPB), patients encounter a complex interplay of inflammation, coagulation, and the foreign surfaces of the extracorporeal circuit, significantly increasing thrombotic risks. Anticoagulation thus becomes crucial in maintaining a balance between preventing life-threatening clots and minimizing bleeding complications. Although CPB has been used since the 1950s, evidence-based guidelines for anticoagulation during CPB have only recently been established. This chapter provides an in-depth exploration of these guidelines, focusing on the monitoring of anticoagulation in CPB. We begin by analyzing the intricate relationship between CPB, coagulation, and inflammation, underscoring its significance in risk assessment. A concise review of evidence-based anticoagulation strategies follows, revisiting medication choices, dosing, and their rationale, building upon the detailed coverage in Chap. 17 . We then delve into a detailed discussion on monitoring and management practices, including both established and emerging point-of-care technologies, examining their strengths, limitations, and optimal use for real-time coagulation status assessment. The chapter concludes by addressing safe and effective strategies for reversing CPB anticoagulation, aiming for a smooth and efficient return to normal hemostasis. This comprehensive approach equips perfusionists and clinicians with the essential knowledge and tools to optimize patient outcomes and ensure a safe, successful surgical experience.