The perinatal period is one of rapid physiological change and evolution, challenging the clinical practitioner to differentiate between normal variation and a pathologic state. Correct interpretation of hematological abnormalities is dependent on accounting for maternal and fetal influences, including maternal pathology, genetic predisposition, and pathologic maternal-fetal interaction. These hematological problems are almost universal in premature and sick neonates but can occur unexpectedly in otherwise healthy term babies. In either case, these diagnoses often require immediate management. Quantitative tests on peripheral blood and bone marrow aspirates/biopsy including morphological analysis require care in collection and processing to reduce artefact and variability; they require experience and expertise in interpretation as values and morphology are highly age dependent. In this chapter, we review some pathologic states that can present in neonates due to bleeding, toxin exposure, and maternal pathology during pregnancy. Additionally, we will discuss conditions that present following delivery, such as coagulopathies, cytopenias, and leukemias.