Traditionally, the diagnosis of schizophrenia has depended on the presence of specific behavioral phenomena assessed by way of behavioral observation and patient symptomatic report. Even though the introduction of explicit diagnostic criteria and structured interviews has improved the reliability of schizophrenia diagnosis, it is still unclear how best to define schizophrenia in order to further etiologic research. This situation persists despite ample evidence that schizophrenia is a heritable brain disorder and the existence of laboratory measures that tap into this neurobiological genetic diathesis. We contend that such laboratory measures can be used to supplement traditional clinical assessment in order to improve the definition of schizophrenia, thereby enhancing research into schizophrenia's origins. Ultimately, this increased understanding of the disorder's etiology should facilitate the development of targeted therapeutic interventions.