Newborn infants in intensive care units, especially those born premature, are at particular risk for blood transfusion adverse effects. Aside improvements in the preparation of specific blood products for the neonatal period, such as multiple packed cells preparations from a single donor for multiple transfusions in premature infants, progress has involved prophylaxis of anemia of prematurity as well. Recombinant human erythropoietin has proven to be beneficial with high range evidence. Also, alternative methods have been proposed to compensate for the delay in the effect of rHuEPO, such as delayed clamping of umbilical cord at birth, or autologous placental blood transfusion. However, a better understanding of the indications of blood transfusion and the provision of practice guidelines may justify a re-evaluation of prophylactic strategies for anemia of prematurity.