In recent years, quantitative studies of the neuropathology of schizophrenia have reignited interest in the cerebral cortex and focused attention on the cellular and subcellular constituents that may be altered in this disease. Findings have ranged from compromised circuitry in prefrontal areas to outright neuronal loss in temporal and cingulate cortices. Herein, we propose that a reduction in interneuronal neuropil in the prefrontal cortex is a prominent feature of cortical pathology in schizophrenia and review the growing evidence for this view from reports of altered neuronal density and immunohistochemical markers in various cortical regions. The emerging picture of neuropathology in schizophrenia is one of subtle changes in cellular architecture and brain circuity that nonetheless have a devastating impact on cortical function.