Hypoxic-ischaemic encephalopathy (HIE) is a leading cause of acquired neonatal brain injury. Assessment of the severity of cerebral injury and likely neurological outcome in infants with HIE is important for determining management and prognosis, for counselling parents, and for selection for neuroprotective trials. The condition of the infant at birth, the severity of HIE, neurophysiological tests, including amplitude-integrated electroencephalography (aEEG), biochemical markers, and neuroimaging have been used to assess prognosis and predict long-term outcome. The predictive accuracy of these indicators in the early postnatal period is modest. Neurophysiological assessment seems to be most helpful during the first 24 to 48 hours after birth whilst magnetic resonance imaging (MRI) seems most informative later. Several biochemical markers, including serum S100β and neuron-specific enolase (NSE), are also associated with HIE but their levels depend on the timing of sampling and their prognostic value is uncertain. Comprehensive neurophysiological assessment and neuroimaging may be limited to specialist centres. Therapeutic hypothermia is now standard care in infants with moderate to severe HIE so it is important to examine the influence of hypothermia on the assessment of prognosis in these infants.