Metachromatic leukodystrophy is a rare inherited disorder of the nervous system. Symptoms initially can present during childhood, adolescence, or adulthood. Psychiatric symptoms, including complex auditory hallucinations and bizarre delusions, are a prominent feature of metachromatic leukodystrophy presenting when the patient is between 12 and 30 years. One hundred twenty-nine published case reports were reviewed, focusing on the presence of psychosis. Psychosis was present in 53% of the published case reports of adolescent and early adult-onset metachromatic leukodystrophy, a much higher prevalence than that seen with other primary neurological disorders. The pathological lesion of metachromatic leukodystrophy is demyelination of the central and peripheral nervous systems, particularly the subfrontal white matter, suggesting that psychosis may result from the disruption of corticocortical and corticosubcortical connections, especially involving the frontal lobes. While similar lesions appear in the infantile, juvenile, and late adult forms of metachromatic leukodystrophy, psychotic symptoms were reported only in those cases presenting in adolescence and young adulthood, suggesting that age is another important neurobiological factor in the development of psychosis.