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A significant body of longitudinal research has followed the offspring of parents with schizophrenia. This article presents a systematic review of 46 separate papers presenting the results of 18 longitudinal studies that have followed children who are at familial high risk of developing psychotic disorders. The studies suggest that these children do show distinct developmental patterns characterized by higher rates of obstetric complication, neurodevelopmental features such as motor and cognitive deficits, and distinctive social behavior. This review summarizes those findings according to child developmental stages. Twelve of the studies followed offspring into adulthood and examined psychiatric diagnoses. From 15% to 40% of children at familial high risk developed psychotic disorders in adulthood. Many also received other psychiatric diagnoses such as mood or anxiety disorders. This combination of results suggests that offspring of parents with schizophrenia are at high risk not just for schizophrenia but, more broadly, for poor developmental and general mental health outcomes. The clinical implications of the findings are discussed, as are new prognostic strategies and potential programs for selective prevention.