As infectious complications from blood transfusion have decreased because of improved donor questionnaires and sophisticated infectious disease blood screening, noninfectious serious hazards of transfusion (NISHOTs) have emerged as the most common complications of transfusion. The category of NISHOTs is very broad, including everything from well-described and categorized transfusion reactions (hemolytic, febrile, septic, and allergic/urticarial/anaphylactic) to lesser known complications. These include mistransfusion, transfusion-related acute lung injury, transfusion-associated circulatory overload, posttransfusion purpura, transfusion-associated graft versus host disease, microchimerism, transfusion-related immunomodulation, alloimmunization, metabolic derangements, coagulopathic complications of massive transfusion, complications from red cell storage lesions, complications from over or undertransfusion, and iron overload. In recent years, NISHOTs have attracted more attention than ever before, both in the lay press and in the scientific community. As the list of potential complications from blood transfusion grows, investigators have focused on the morbidity and mortality of liberal versus restrictive red blood cell transfusion, as well as the potential dangers of transfusing "older" versus "younger" blood. In this article, we review NISHOTs, focusing on the most recent concerns and literature.