Diabetes has a marked effect on brain function and structure in children and adolescents. As a group, diabetic children are more likely to perform more poorly than their nondiabetic peers in the classroom and earn lower scores on measures of academic achievement and verbal intelligence. Specialized neuropsychological testing reveals evidence of dysfunction in a variety of cognitive domains, including sustained attention, visuoperceptual skills, and psychomotor speed. Children diagnosed early in life – before 7 years of age – appear to be most vulnerable, showing impairments on virtually all types of cognitive tests, with learning and memory skills being particularly affected. Results from neurophysiological, cerebrovascular, and neuroimaging studies also show evidence of CNS anomalies. Earlier research attributed diabetes-associated brain dysfunction to episodes of recurrent hypoglycemia, but more recent studies have generally failed to find strong support for that view. While there is growing evidence to suggest that elevated blood glucose levels may play an important role in the development of cognitive dysfunction in diabetic adults, there remains little compelling data for that possibility from pediatric studies, in part because of the many methodological shortcomings inherent in much of this research. In a systematic, critical review of the extant pediatric literature, this chapter addresses a variety of issues: Is it possible to identify one or more well-defined neurocognitive phenotypes characteristic of diabetes in childhood? Why – from developmental, biomedical, and psychosocial perspectives – are some diabetic children more likely to develop neurocognitive deficits? What is the pathophysiological basis for these brain anomalies?