A consistent and organized transition from embryonic to fetal to adult hemoglobin (Hgb) occurs during human fetal development. Hgb concentrations gradually increase, averaging 18 g/dL (180 g/L) by 40 weeks' gestation. The ability to deliver oxygen to tissues in the fetus and neonate is primarily determined by the percentage of fetal versus adult Hgb and the concentration of 2,3 diphosphoglycerate (2,3-DPG). Studies continue to evaluate the relationship between Hgb concentrations and oxygen delivery in neonates to determine what Hgb concentrations best meet the needs of a wide variety of clinical situations from the critically ill extremely low-birthweight infant to the stable growing preterm infant. Biochemical interactions between nitric oxide (NO) and Hgb beyond the production of methemoglobin do occur and may be a source of deliverable NO to the microcirculation under hypoxic conditions.