Preterm infants are more liable to suffer from anemia, as 90% of extremely low birth weight infants receive red blood cell transfusion. When to receive red blood cell transfusion is not well defined until now, even the complications and hazards resulting from the transfusion of adult red blood cell into the premature circulation is still a matter of debate. In this review, fetal erythropoiesis and the unique pathophysiology of anemia of prematurity is discussed, different meta-analysis studies are presented regarding liberal (high hemoglobin threshold) or restrictive (low hemoglobin threshold) transfusion protocols, early or late transfusion preferences. To clarify the picture of this, everyday decision neonatologists need to take, whether or not to give this premature infant a red packed cell transfusion, which may affect the life of this infant indefinitely. Until now, no fixed guidelines are present regarding when to transfuse anemia and still dependent on expert opinion and center experience.