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The literature concerning brain damage due to hydrocephalus, especially in children and animal models, is reviewed. The following conclusions are reached:1. Hydrocephalus has a deleterious effect on brain that is dependent on magnitude and duration of ventriculomegaly and modified by the age of onset.2. Animal models have many histopathological similarities to humans and can be used to understand the pathogenesis of brain damage.3. Periventricular axons and myelin are the primary targets of injury. The pathogenesis has similarities to traumatic and ischemic white matter injury. Secondary changes in neurons reflect compensation to the stress or ultimately the disconnection.4. Altered efflux of extracellular fluid could result in accumulation of waste products that might interfere with neuron function. Further research is needed in this as well as the blood-brain barrier in hydrocephalus.5. Some, but not all, of the changes are preventable by shunting CSF. However, axon loss cannot be reversed, therefore shunting in a given case must be considered carefully.6. Experimental work has so far failed to show any benefit in reducing CSF production. Pharmacologic protection of the brain, at least as a temporary measure, holds some promise but more pre-clinical research is required.