Understanding how prenatal serotonin reuptake inhibitors (SRIs) influence early brain development can provide critical clues to how early life experience programs developing neural systems that might contribute to risks for illness across the life span. To date, no gross SRI-related neuroteratogenic effects have been identified, but evidence of subtle functional behavioral disturbances associated with fetal SRI exposure are emerging. Although some outcomes reflect a “main effect” for the SRI exposure, childhood development beyond infancy appears typical or continues to be influenced by life with a mother with a mood disturbance. Research shows that not all infants and children are equally affected; thus appreciating the effects of prenatal and postnatal maternal mental illness and of genetic variations that influence early serotonin signaling offers critical new insights into factors that contribute to developmental risk, plasticity, and resiliency in children with prenatal SRI exposure. Such a developmental perspective should lead us to understand what heightens or lessens neurodevelopmental vulnerability, thereby optimizing maternal pharmacotherapy and identifying who benefits and is least likely to experience neurobehavioral disturbances. Birth Defects Research (Part A) 94:651–659, 2012. © 2012 Wiley Periodicals, Inc.