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The prediction of neurologic outcome is a fundamental concern in the resuscitation of patients with severe brain injury.To provide an evidence-based update on neurologic prognosis following traumatic brain injury and hypoxic-ischemic encephalopathy after cardiac arrest.Search of the PubMed database and manual review of bibliographies from selected articles to identify original data relating to prognostic methods and outcome prediction models in patients with neurologic trauma or hypoxic-ischemic encephalopathy.Articles were scrutinized regarding study design, population evaluated, interventions, outcomes, and limitations. Outcome prediction in severe brain injury is reliant on features of the neurologic examination, anatomical and physiological changes identified with CT and MRI, abnormalities detected with electroencephalography and evoked potentials, and physiological and biochemical derangements at both the brain and systemic levels. Use of such information in univariable association studies generally lacks specificity in classifying neurologic outcome. Furthermore, the accuracy of established prognostic classifiers may be affected by the introduction of outcome-modifying interventions, such as therapeutic hypothermia following cardiac arrest. Although greater specificity may be achieved with scoring systems derived from multivariable models, they generally fail to predict outcome with sufficient accuracy to be meaningful at the single patient level. Discriminative models which integrate knowledge of genetic determinants and biologic processes governing both injury and repair and account for the effects of resuscitative and rehabilitative care are needed.