This chapter comprehensively describes not only the molecular origin of disorders of red blood cells, coagulation factors, fibrinolytic proteins, and platelets but also the clinical manifestations, diagnostic procedures, therapeutic approaches, and management of affected patients. Genetic mutations of the red cell membrane and enzymes resulting in severe hemolytic anemia are discussed, including hereditary spherocytosis, elliptocytosis, stomatocytosis, G6PD deficiency and pyruvate kinase deficiency. The genotypes and phenotypes of hemoglobinopathies are reviewed including sickle cell anemia, alpha thalassemia and beta thalassemia. The genetic forms of megaloblastic anemia (e.g., deficiency of intrinsic factor, transcobalamin) are presented. Molecular abnormalities of the coagulation cascade, anticoagulation pathway, and fibrinolysis are elucidated, particularly the hemophilias, von Willebrand disease, antithrombin III deficiency, factor V Leiden, protein C/S deficiency, and plasminogen deficiency. This chapter concludes with a discussion of inherited platelet problems such as Glanzmann thrombasthenia, gray platelet syndrome, and Bernard Soulier syndrome, and how clinicians diagnose and manage patients with these rare disorders.