The core features of schizophrenia include deficits in cognitive processes mediated by the circuitry of the dorsolateral prefrontal cortex (DLPFC). These deficits are associated with a range of molecular and morphological alterations in the DLPFC, each of which could be a cause, consequence, or compensation in relation to other changes, and thus reflect the neuroplasticity of the brain in response to the underlying disease process. In this review, we consider disturbances in excitatory, inhibitory, and modulatory connections of DLPFC circuitry from the perspective of disease-and development-related neuroplasticity and discuss their implications for the identification of novel therapeutic targets.