Behavioural changes and cognitive impairments in schizophrenia have been linked to disturbances of complex neural networks involving both frontal and subcortical systems. Current literature has emphasised the role of the dorso-lateral prefrontal cortex (DLPFC) and its connections with hippocampus in the pathogenesis of schizophrenia. Based on a review of the literature, this paper examines other possible prefrontal areas that contribute to the manifestations of schizophrenia. We focus on the orbito-frontal cortex (OFC) and argue that it also plays an important role in the behavioural manifestations, symptoms and cognitive impairments observed in schizophrenia. The importance of fronto-striato-thalamic circuits connecting these prefrontal sites with subcortical structures is examined and the relevance of functions specific to these circuits or their components are briefly discussed. The subdivision of the functions of the prefrontal cortex into 'prefrontal' syndromes are examined and related to both the behavioural and symptom-based syndromes of schizophrenia. Possible dissociations of function of the various prefrontal syndromes and the relationship of these to schizophrenia syndromes may provide clues to the underlying neurobiology of schizophrenia. The use of tasks deemed specific to DLPFC and OFC networks may be useful as probes to examine the integrity of these circuits. We discuss such 'circuit-specific' tasks including delayed response, delayed alternation and object alternation tasks derived from the animal literature and other tasks such as olfactory identification ability. This approach raises the possibility that a number of prefrontal cortical areas and their subcortical connections are important in accounting for the heterogeneity of schizophrenia.