Immunohematology encompasses a broad array of clinical disorders in which immune reactions are involved in the pathogenesis of hematologic diseases. Immune reactions can involve the formed elements of the blood, producing hemolytic anemia, thrombocytopenia, or neutropenia. Autoimmune phenomena and drug-induced reactions are the most common mechanisms. In newborns, maternal antibodies can cross the placenta and destroy red blood cells, platelets, or neutrophils. Immune reactions can also occur during transfusion of blood products, leading to hemolysis, febrile reactions, allergic reactions, and lung injury. The role of leukocytes and cytokines released during blood component storage in mediating febrile transfusion reactions has prompted the increased use of leukocyte-reduced components. Immune reactions can occur to soluble clotting factors and can produce bleeding or thrombosis. Finally, immunohematologic features of B-cell disorders are considered.