Postmortem neuropathological investigations in the last half decade provide increasing evidence compatible with a neurodevelopmental defect in schizophrenia. Basic and clinical data support hypotheses suggesting that disturbances in neurodevelopment in schizophrenia may involve the cortical subplate and a theorized second trimester "window of vulnerability". The focus of this paper is on (1) selected methodological issues involved in the collection, analyses and preservation of human postmortem brain tissue; (2) a review of evidence showing morphological defects particularly in prefrontal cortical regions of the schizophrenic brain; and (3) potential future research directions.