The number of studies documenting the long-term morbidity of CNS treatment has increased dramatically in recent years. Cranial irradiation, in particular, has been associated with cognitive deficits and neuroanatomic pathology. Children who are treated at an early age and individuals who receive higher doses (2,400 cGy or greater) appear to be at greatest risk for these sequelae. Much more research on the pathogenesis of delayed injury following CNS treatment is needed. Although several compelling mechanisms have been proposed, little empirical evidence is available. This knowledge is essential to the identification of agents that may protect normal brain tissue from injury. Even less is known about the effects of age at time of treatment, type of treatment (radiation v chemotherapy), or dose of radiation in relation to delayed injury. Of utmost importance are studies that will establish the predictive relationship between brain injury and cognitive deficits. This would allow clinicians to predict patients who are at risk for cognitive impairment in order to institute appropriate preventive or remedial interventions.