Hematopoiesis in the fetus and neonate is in a constant state of flux and evolution as the newborn adapts to a new physiological milieu. Hematological problems may present during this period as a result of a genetic defect, immaturity, or stress, and present a major diagnostic and therapeutic challenge to the neonatologist and hematologist alike. Advances in molecular techniques have allowed the elucidation of the cellular mechanisms that give rise to some of these disorders of the hematopoietic system. It is hoped that this chapter will give the reader a broad understanding of the major hematological disorders seen in the neonatal period, especially those involving platelets, white cells, red cells, and clotting proteins.