The vague relationship between diagnosis, underlying etiology and a rudimentary understanding of the pathophysiology of psychosis, particularly schizophrenia, has made it difficult to develop and validate suitable disease models for such disorders. Despite recent technological advancements, animal models have yet to yield a revolutionary treatment for schizophrenia. Refinement and standardization of assessment methods in the preclinical domain and streamlining of concepts from which animal models are generated are required, particularly in relation to models that recapitulate cognitive and negative symptoms of schizophrenia. In this review, caveats of current treatments for schizophrenia and current animal modeling strategies are examined in the context of their validity and potential for discovery of novel therapies, and finally, future prospects for the field are considered.