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Cognitive deficits are a core feature of schizophrenia. Among these deficits, working memory impairment is considered a central cognitive impairment in schizophrenia. The prefrontal cortex, a region critical for working memory performance, has been demonstrated as a critical liability region in schizophrenia. As yet, there are no standardized treatment options for working memory deficits in schizophrenia. In this review, we summarize the neuronal basis for working memory impairment in schizophrenia, including dysfunction in prefrontal signaling pathways (e.g., γ-aminobutyric acid transmission) and neural network synchrony (e.g., gamma/theta oscillations). We discuss therapeutic strategies for working memory dysfunction such as pharmacological agents, cognitive remediation therapy, and repetitive transcranial magnetic stimulation. Despite the drawbacks of current approaches, the advances in neurobiological and translational treatment strategies suggest that clinical application of these methods will occur in the near future., (Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)