Abstract: All neonates experience a downtrend in their hematocrit values immediately following the birth through normal falls in erythropoietin (Epo) production, transition to adult hemoglobin, and hemodilution with somatic growth. However, this drop is more pronounced in critically ill and preterm neonates and can lead to potentially pathologic anemia that impairs tissue oxygen delivery. In this review, we highlight the mechanisms underlying physiologic anemia and anemia of prema-turity and briefly review the evidence for the treatment of anemia in the neonatal population, includ-ing the use of red blood cell transfusions, erythropoietic stimulating agents, and iron supplementa-tion.