The frontal lobe and, especially, the prefrontal cortex , together with the temporolimbic structures and the ganglia of the base, are three widely interconnected brain systems, which have been involved in the pathophysiology of schizophrenia since the time of Emil. Kraepelin, to the point of considering schizophrenia as a fronto-temporolimbic disease. In recent decades, multiple converging lines of research have shown that in schizophrenia there is a dysfunction of the frontal cortex. The defective or negative psychotic symptoms of schizophrenia resemble those of patients with traumatic, vascular or degenerative lesions in the frontal lobe.