Preterm infants, especially those with extremely low birth weight (ELBW) are exposed to frequent blood draws as part of their care in the neonatal intensive care unit. ELBW infants develop the anemia of prematurity (AOP), a hypo-proliferative anemia marked by inadequate production of erythropoietin (Epo). Treatment of AOP includes red blood cell transfusions, which are given to preterm infants based on indications and guidelines (hematocrit/hemoglobin levels, ventilation and oxygen need, apneas and bradycardias, poor weight gain) that are relatively non-specific. In this article we review recent studies evaluating transfusion guidelines, discuss ways to decrease phlebotomy losses and examine the use of red cell growth factors such as Epo in preventing and treating anemia in preterm infants.