Critically ill patients form a population with a special necessity for allogeneic blood transfusions (AT). Multiple observational studies, most done in patients undergoing surgery for colorectal cancer, have associated AT with a higher rate of postoperative infections. This association has also been studied and proven in critically ill patients undergoing cardiac surgery, suffering polytrauma, septicemia, and transplantation. These studies have included local infections (the surgical wound), infections distant from the surgical site (pneumonia, urinary tract infection), and systemic infections (septicemia). The transfusion-related immunomodulation seems to be the cause of the immunologic changes in the recipient, leading to the acquirement of postoperative infections, the upregulation of the humoral immune response (Th2), and the downregulation of the cellular immune response (Th1). Observational studies can, however, prove an association that is not necessarily causal between transfusion and postoperative infection. The randomized, controlled trials designed to prove a causal relationship have yielded contradictory results. In three of these studies, the rate of infection was greater in patients transfused with allogeneic blood, whereas in the other three studies, the infection rate was not greater. The meta-analyses did not demonstrate a causal relationship between infection and transfusion. In summary, the allogeneic transfusion of packed red blood cells could be involved in a greater risk for postoperative infection in critically ill patients. Awaiting the confirmation of a causal relationship, the possibility of a transfusion-mediated postoperative infection should make AT a considered risk factor for infection.