A large body of evidence has implicated abnormal functioning of the prefrontal cortex (PFC) in the pathophysiology of schizophrenia (Robbins 1996; Andreasen et al. 1997; Winterer and Wvneinberger 2004; Lewis and Moghaddam 2006). These abnormalities are found at molecular and functional levels and are thought to be the basis of cognitive deficits in individuals with schizophrenia. However, little is known about the physiological mechanisms that contribute to this malfunction. Here we review some of the literature that points to PFC abnormalities in schizophrenia and recent theories that unify the multimodal functional and postmortem findings in schizophrenia.