Schizophrenia is a multithetic disorder in which the diverse signs and illness symptoms arise as a result of dysfunction in a number of brain regions. Individuals with schizophrenia perform poorly on cognitive tasks that require the use of working memory: the ability to maintain information "on line" in order to guide behavior. Both imaging and postmortem studies have revealed abnormalities in the thalamus of subjects with schizophrenia. Evidence for abnormalities in mediodorsal nucleus (MDN) to dorsolateral prefrontal cortex (DLPFC) projections includes reductions of both pre- and postsynaptic markers for the axons. The discussed findings suggest that alterations in MDN-DLPFC circuitry play a critical role in the pathophysiology of cognitive dysfunction in schizophrenia. Relatively few studies have examined details of the organization of MDN-DLPFC circuitry in primates, and much of our understanding of the functional attributes of this circuitry represents reasonable but speculative extrapolation from studies of sensory thalamic systems.