Many of the social, economic, and political problems facing people with schizophrenia are due to a misconception in the community that schizophrenia is not a biologically based disease but a myth. Because the diagnosis is based on self-reported symptoms, it is difficult for many people to acknowledge that schizophrenia is real. One goal of psychophysiological research has been to anchor both diagnosis and symptoms in biological reality. Reduction of the amplitude of the P300 component of the event-related potential (ERP) is the most replicable biological marker of the disease. Data are presented suggesting that P300 is both a state and a trait marker of the disease and may be sensitive to the progressive/degenerative course of the disease. Although the P300 tracks changes in clinical symptoms, it remains reduced even in patients in relative remission. P300 amplitude reduction is related to enduring negative symptoms, waning of attention, and gray matter volume deficits. ERP components other than P300 can also manifest the biological reality of various symptoms of the disease.