Schizophrenia is a complex genetic disease with a prevalence rate of 1% in the general population. Schizotypal personality disorder (SPD) occurs in up to 3% of the population, and these subjects are phenomenologically and perhaps genotypically related to schizophrenia. The diagnosis of SPD was empirically derived based on the symptoms of individuals with a genetic relationship to schizophrenia patients and SPD may be a more common phenotypic expression of a schizophrenia-related diathesis than is schizophrenia itself. Family-genetic studies have determined that (1) relatives of schizophrenic patients have an increased risk of SPD and (2) relatives of SPD subjects have increased the rates of both schizophrenia and SPD. Because SPD subjects do not typically have the confounding effects of a chronic illness, long-term hospitalization or chronic neuroleptic treatment, they are ideal for the study of the proposed trait-related vulnerability markers in schizophrenia spectrum individuals. The study of vulnerability markers in SPD subjects has become increasingly important because it provides a means of assessing phenotypic traits that may not be evident clinically. By combining multiple inhibitory/gating information processing measures, it may be possible to identify a subgroup of SPD subjects with multiple inhibitory deficits who are phenotypically most similar to patients with schizophrenia. Composite phenotypes can also be developed, which increase the probability of identifying the complex genetic architecture of schizophrenia spectrum disorders, which interact with nongenetic protective and exacerbating factors.