Dysfunction of the prefrontal cortex (PFC) in schizophrenia has been suspected based on observations from clinical, neuropsychological and neuroimaging studies. Since the PFC receives a dense dopaminergic innervation, abnormalities of the mesocortical dopamine system have been proposed to contribute to the pathophysiology of schizophrenia. In this review, aspects of the anatomy, physiology and pharmacology of the mesencephalic-frontal cortical dopamine system as they may relate to schizophrenia are described, and evidence for altered dopaminergic neurotransmission in the frontal cortex of schizophrenic patients is presented.