In the developed world, most of the reported complications of transfusion have an immunological basis. Although the media and the public are worried about the infectious risks of transfusion, hemovigilance reports show that antigen–antibody reactions are responsible for the vast majority of acute and delayed transfusion reactions. Among the immediate complications of transfusion, the most common and serious are intravascular hemolytic transfusion reactions because of ABO incompatibility caused by giving the wrong blood to a patient (e.g. group A blood to a group O recipient). Fortunately, the vast majority of ABO-incompatible transfusions do not lead to major morbidity or mortality. Another important cause of severe immediate transfusion reactions is transfusion-related acute lung injury (TRALI), caused by white cell antibodies in donor plasma. The most common, although not severe, acute tansfusion reactions are urticaria and febrile, nonhemolytic, mostly preventable by leukodepletion and leukoreduction. Delayed transfusion reactions are: (i) hemolytic, caused by anamestic responses to red cell antigens, causing hemolysis days after the transfusion; (ii) post-transfusion purpura, caused by an anmnestic response to platelet antigens; (iii) graft-versus-host disease, caused by engrafted donor lymphocyte reacting against the recipient; and (iv) immunological refractoriness to platelet transfusions, caused mostly by human leukocyte antigen antibodies destroying transfused platelets. The diagnosis of most of these complications can now be made by immunohematologists, with the aid of specialist reference laboratories, thus enabling prompt therapy as required.