The risk of acquiring a transfusion-transmitted infection has declined in recent years. However, after human immunodeficiency virus and hepatitis B and C virus transmission were successfully reduced, new pathogens are threatening the safety of the blood supply, especially in the face of rising numbers of immunocompromised transfusion recipients. Despite new standards in the manufacture and storage of blood products, bacterial contamination still remains a considerable cause of transfusion-related morbidity and mortality. Better allograft survival in kidney transplant patients and higher cancer recurrence rate in surgical oncology patients after allogeneic blood transfusions highlighted a previously underestimated side-effect: transfusion-related immunomodulation (TRIM). The precise pathomechanism still remains uncertain; however, its mostly deleterious effects--such as a higher incidence of postoperative or nosocomial infections--is increasingly accepted. Although transfusion-related immunomodulation is thought to be mediated mainly by donor white blood cells, the benefit of leukoreduction on overall mortality and on infectious complications is highly debatable.