Recent advances in research on schizophrenia have significantly changed the manner in which translational research is being conducted in this field. Although there is a lack of gross morphological change observed in the brains of schizophrenic patients, there is substantial evidence that this disorder is one of impaired synaptic connectivity, which has been observed in numerous humans postmortem as well as in functional and structural brain imaging studies. This chapter outlines the major neuropathological and behavioral abnormalities associated with schizophrenia. It discusses the risk genes most implicated in the pathophysiology of schizophrenia and outlines their roles in regulating aspects of neuroplasticity thought to be perturbed in this disease. The chapter describes the pharmacological and genetic animal models that are being used in translational research. It highlights novel therapeutic targets currently being investigated for treating schizophrenia.