In addition to the known adverse effects of red blood cell transfusion, evidence suggests that transfusion with allogeneic red blood cells in itself may increase mortality, risk of infection and even cancer recurrence rates. Among possible mechanisms to explain this effect are transfusion-related immune modulation and storage lesions. However, anaemia may also increase mortality and the risk of anaemia should be balanced against the risks of transfusion. Further properly designed and powered studies are needed to clarify the beneficial and harmful effects of red blood cell transfusion in well-defined patient categories.