Our aim was to document changes in the evaluation and prognosis of term-born infants with neonatal encephalopathy of hypoxic-ischemic origin, with particular reference to our own experiences and influences, and to summarize the debate on causation and the relative importance of antenatal and perinatal factors. High quality neonatal cranial ultrasound and magnetic resonance imaging and spectroscopy have enabled the accurate early visualization of different patterns of hypoxic-ischemic brain injury and prediction of their associated outcomes. Long-term follow-up shows that cognitive and memory difficulties may follow even in children without motor deficits. The very early use of electrophysiologic methods has allowed broad prognostic categorization of infants when this is not possible from clinical assessment or imaging, providing a rationale for entry into intervention trials, such as therapeutic hypothermia. This work has also shown that most of these infants have evidence of acute hypoxic-ischemic brain injury that explains their symptoms and outcomes.