A problem confronting the search for psychopathology-related genes concerns the difficulty identifying gene carriers. Psychiatric diagnosis provides imperfect identification of affected individuals, and unaffected gene carriers go undetected. Psychophysiological measures may assist molecular genetic investigations by indicating genetic susceptibility for psychopathology, thus increasing the probability of identifying affected and unaffected gene carriers. Research strategies based on these premises are applied to the study of psychoactive substance use disorders and schizophrenia. Data are presented illustrating (1) that individual differences in inhibitory control involving autonomic and antisaccade eye movement measures and the P3 component of the event-related potential may be sensitive to susceptibility for substance use disorders, and (2) that eye tracking variables may identify genetic risk for schizophrenia.