A large number of infants are born each year with biologic or environmental risk factors that put them at increased risk for developmental disability, although most do not go on to have major disabilities. Some risk factors, for example, intraparenchymal hemorrhage, periventricular cysts, encephalomalacia, and abnormal neurodevelopmental examination, carry a much higher risk of developmental disability than others. There is much overlap among risk factors, and infants with multiple risk factors generally have a greater risk of disability than infants with just a single risk factor. All high-risk infants should receive careful pediatric follow-up that includes developmental screening, but efficient use of so far quite limited resources argues for selection of the highest risk infants for comprehensive developmental follow-up or early intervention programs. A system of tracking and monitoring high-risk infants during infancy and childhood would allow for early identification of developmental delay and appropriate referral for community resources.