The developing nervous systems is subject to damage from lack of vital substances necessary for normal maturation and function as well as from trauma or a variety of toxins and infectious agents. By far, the most important of these is inadequate oxygen delivery to the fetus in utero, and/or during the intrapartum and/or early neonatal period. Many types of lesions have been described under the rubric of hypoxic-ischemic encephalopathy, a major proportion of which are found only in the immature nervous system and essentially are never seen later in life. Moreover, a large number are primarily hemorrhagic rather than ischemic in character. The unique character and distribution of these lesions results from a collision of the changing anatomy of the developing nervous system and pathophysiological factors afflicting the immature organism. Whereas the majority of hypoxic-ischemic lesions in the fetus/neonate fall into this group, abnormalities characteristically found in the mature nervous system are also seen. Recognition of the anatomic and physiological features peculiar to the developing nervous system will assist in diagnosis of hypoxic-ischemic damage peculiar to the fetus and neonate.