Evidence from diverse avenues of research has highlighted abnormalities in the anatomy, physiology, and function of medial temporal lobe structures in schizophrenia. Clinical similarities between schizophrenia and psychotic disorders associated with temporal lobe lesions have been recognized for decades. Neuropsychological studies have found selective impairments in learning and memory in schizophrenia consistent with medial temporal lobe dysfunction. Neuroimaging studies have identified medial temporal lobe abnormalities that have been correlated with clinical features. Postmortem findings in the hippocampus and entorhinal cortex have included differences in neuron density, size, and arrangement; abnormalities in synapse-related proteins; alterations in monoaminergic and glutamatergic innervation and receptor distribution; and abnormalities in the expression of cytoskeletal proteins. These findings appear most consistent with models of aberrant development of medial temporal lobe structures in schizophrenia.