Schizophrenia appears to be a neurodevelopmental disorder involving dysfunctional prefrontal and temporal cortical neural systems. Recent data implicate presynaptic changes in subcortical dopamine neurotransmission, as well as alterations in cortical glutamatergic and GABAergic systems. Functional neuroimaging studies, combined with tests of neuropsychological function, suggest that cortical abnormalities underlie the cognitive deficits associated with schizophrenia. These deficits appear to account for much of the psychosocial dysfunction of schizophrenia and are particularly treatment refractory. Genetic studies have implicated several minor susceptibility loci; however, the clinical impact of these loci on the neurobiology of schizophrenia is still unclear. The use of neurobiological traits as phenotypes, such as cognitive deficits and cortical abnormalities, in genetic linkage studies may facilitate the identification of loci that underlie the most debilitating features of schizophrenia.