Prospective studies of young relatives at risk for schizophrenia can shed light on the possible premorbid precursors of the disease. Ongoing studies in Pittsburgh suggest that young non-psychotic high risk relatives have neurobehavioral, brain structural, physiological, and neurochemical deficits that may date back to childhood or earlier. We summarize these data, review the relevant literature in this emerging field, and provide some new data suggesting alterations in sleep architecture in young relatives at risk for schizophrenia. Collectively, such data are likely to help us to predict the eventual emergence of schizophrenia, schizophrenia spectrum or non-spectrum psychopathology.