Hematologic values in neonates differ significantly from those in older children and adults. Quantitative and qualitative differences are present as a reflection of the developmental changes during fetal hematopoiesis and, so, correlate with gestational age. At birth, the hemoglobin, mean corpuscular volume, and WBC counts of term newborns are significantly higher than those of older children and adults, and in preterm neonates the differences are even more pronounced. This review explores these differences and the major factors that account for them from the hematology laboratory standpoint. After a discussion of the developmental hematopoiesis and normal hematologic values in term and preterm neonates, important preanalytic factors, such as limited blood availability, effect of sampling site, and violent crying, and analytic interferences are examined. Finally, the review addresses resulting challenges in interpretation of hematologic test results in term and preterm neonates, especially issues surrounding neonatal reference intervals and critical value reporting, and suggests possible solutions.