Schizophrenia has traditionally been viewed as a psychotic disorder with onset in adolescence or early adulthood and a deteriorating course. Over the past decade, the authors have been studying patients meeting DSM-III-R as well as specified research criteria for late-onset schizophrenia (onset after age 45) and several comparison groups with psychiatric, neurologic, neuropsychologic, brain-imaging, psychophysiological, and psychosocial assessments. Results to date suggest a number of similarities and differences between late-onset schizophrenia and comparison groups of other older patients with psychoses (including earlier-onset schizophrenia). Later-onset schizophrenia is probably a neurobiologically distinct subtype of schizophrenia. Differential involvement of cortico-striato-pallido-thalamic circuitry may explain differences in age at onset. The authors propose a new conceptual model for level of functioning at different stages of life in late-onset schizophrenia.