In this first of a three-part series on hypoxia in the term newborn, the emphasis is on cardiopulmonary adaptation of the newborn. This article includes definitions and features of neonatal hypoxia and reviews structural abnormalities of the heart and great vessels, along with pulmonary hypertension. During the transitional phase from intrauterine to extrauterine life, newborn infants require close monitoring in order to recognize and address abnormalities in adaptation. The evaluation of the hypoxic infant is one of the most common problems for the pediatric clinician; although there are several common causes for newborn cyanosis, myriad disorders spanning all organ systems exist as possibilities etiologies. Knowledge of the breadth of feasible diagnoses and a systematic approach to the assessment of these term newborns are essential for accurate diagnosis, treatment, and referral.