This chapter explores into the complex considerations surrounding hematocrit and transfusion management during cardiopulmonary bypass (CPB). It discusses the delicate balance between the benefits and risks of erythrocyte transfusion during CPB, highlighting the association of both anemia and transfusion with increased morbidity and mortality. The chapter explores the consequences of hemodilution during CPB, particularly its impact on cerebral blood flow and oxygen-carrying capacity, and outlines strategies for managing hematocrit levels to optimize patient outcomes. It also reviews the transfusion thresholds for adults and children, emphasizing the variability in these thresholds based on numerous factors, including the type of surgery and patient-specific characteristics. Overall, this chapter provides a comprehensive overview of hematocrit and transfusion management during CPB, integrating current research findings with practical clinical applications.