Although much information has been accumulated about the clinical use of Epo in preterm infants, many questions remain unanswered. The evolution of clinical practice in the care of extremely ill, preterm infants continues to affect the number of transfusions required during hospitalization. Decreasing phlebotomy losses and instituting standardized transfusion guidelines have both been shown significantly to decrease the transfusion requirements of preterm infants. The administration of Epo likely decreases transfusion need even further; however, the direct impact of each of these actions has not been studied prospectively. It is likely that the combination of instituting rigorous and standardized transfusion guidelines, decreasing phlebotomy losses, and the appropriate use of Epo will have the greatest impact in decreasing transfusion requirements in all preterm and term neonates, regardless of the cause of their anemia.