The long-term prognosis of the newborn infant destined for neurosurgery may depend in large part on preexisting neurologic disturbances. The ability to delineate preoperatively the likely long-term neurologic outcome of such infants facilitates the formulation of optimal interventions and the prediction of likely benefit of a specific intervention and addresses parental concerns for the likely outcome with and without neurosurgical intervention. This article describes two fundamental approaches, using clinical observations or laboratory investigations for delineating such a prognosis. Clinically important factors include the underlying cause, the extent of associated parenchymal injury, and the nature of comorbid factors, particularly those of cerebrovascular and dysgenetic origin. Other important prognostic factors include the age at presentation, the rate of progression, and timing of intervention. The use and limitations of current structural brain imaging, electrophysiologic and perfusion studies, and newer neurodiagnostic techniques are discussed.