Patients presenting with blood disorders requiring cardiopulmonary bypass (CPB) pose unique management challenges in regard to both preoperative optimization and perioperative management. A firm understanding of the breadth of blood disorders—including their etiologies, pathophysiology, and potential complications—is crucial for the successful conduct of CPB and improving patient outcomes. This chapter delves into various blood disorders and their specific considerations for CPB and cardiac surgery. We will discuss the complexities involved in surgical planning, including preoperative assessment, intraoperative management, and postoperative care. Additionally, we will explore how these disorders influence blood clotting, platelet function, and overall hemostasis. Specific disorders to be examined include red blood cell disorders (including RBC enzyme deficiencies, hemoglobinopathies, erythrocytosis, and hemochromatosis), inherited bleeding disorders (such as hemophilia and Von Willebrand disease), inherited and acquired clotting disorders, platelet disorders such as thrombotic thrombocytopenic purpura (TTP) and immune thrombocytopenia (ITP), and myeloproliferative diseases. The objectives of this chapter are to outline the challenges and strategies for managing these conditions in the context of CPB, detail diagnostic approaches including essential laboratory tests for diagnosis and risk stratification, and discuss treatment protocols involving pharmacological agents and surgical interventions. A comprehensive grasp of these blood disorders in the setting of CPB enables clinicians to optimize care for these complex patients, ensuring safety during surgery and fostering improved recovery processes.