The authors first review current evidence concerning abnormalities of brain structure and function in schizophrenia and interpret them within a "network" pathophysiological model of the disorder. This information is then placed within a contemporary neurodevelopmental framework that "roots" the illness in adverse events during early pregnancy, which result in a developmentally compromised nervous system. They then consider the controversy as to whether the subsequent expression of psychosis reflects an active morbid process and, in a more general sense, whether the disorder is characterized by subsequent progression and clinical deterioration. The authors argue that the developmental and progressive models should not be considered in an either-or manner, since this perspective is not logical and favors nihilistic approaches to intervention and treatment, but rather should be integrated within a lifetime trajectory model. Finally, implications for current psychiatric practice are considered.