The developmental origins of health and disease hypothesis applied to neurodevelopmental outcomes asserts that the fetal origins of future development are relevant to mental health. There is a third pathway for the familial inheritance of risk for psychiatric illness beyond shared genes and the quality of parental care: the impact of pregnant women's distress-defined broadly to include perceived stress, life events, depression, and anxiety-on fetal and infant brain-behavior development. We discuss epidemiological and observational clinical data demonstrating that maternal distress is associated with children's increased risk for psychopathology: For example, high maternal anxiety is associated with a twofold increase in the risk of probable mental disorder in children. We review several biological systems hypothesized to be mechanisms by which maternal distress affects fetal and child brain and behavior development, as well as the clinical implications of studies of the developmental origins of health and disease that focus on maternal distress. Development and parenting begin before birth.