Schizophrenia is a devastating mental illness affecting millions worldwide with significant financial and emotional burdens for afflicted persons, their families, and society. Considering schizophrenia as a disorder of neuroplasticity permits integration of competing neurochemical and neurodevelopmental hypotheses. Recent advances have linked the pathophysiology of schizophrenia with abnormalities of the glutamate neurotransmitter system. Elements of glutamatergic neurotransmission implicated in schizophrenia, including glutamate receptors and receptor-associated molecules, have critical roles in long-term potentiation, a molecular correlate of neuroplasticity. We suggest that schizophrenia can be considered a disorder of plasticity, associated with molecular abnormalities of the glutamate synapse. Copyright 2004, Elsevier Inc. All rights reserved.