The scope of preschool children with biological risk and social disadvantage is large and includes over 1 million (28%) newborns per year. Currently in 1996, 7% of children are born with low birth weight, 1% are born with very low birth weight, 20% have alcohol exposure, and 10% have other drug exposure. Poverty is dynamic and impacts on 25% of children less than 6 years old with increased frequency in children who are minority, have mothers with less than a high school education, or are unmarried. There has been a markedly increased survival in very low birth weight and extremely low birth weight infants in the past 10 years. Outcomes of these neonatal populations reveals that parenchymal brain injury is the major predictor of cerebral palsy which occurs in 7% to 10% of very low birth weight survivors. However, poverty is the major predictor of low IQ. Fetal alcohol syndrome occurs in 1.9 per 1,000 births and is most often associated with mild mental retardation and educational underachievement. Studies investigating cocaine revealed that it is a multifactorial problem overlapping with polysubstance abuse and other risk factors for social disadvantage. The overwhelming number of children do not have cerebral palsy or severe mental retardation. The long-term impact is more subtle and needs more systematic analysis as well as critical evaluation of cognitive impairments and educational under-achievement. Hypoxic ischemic encephalopathy (HIE) cannot be determined by one biological measure. Though multiple disability occurs in 70% of children with Sarnat stage 3 HIE, 30% of survivors are not disabled. Children with mild to moderate HIE have long-term outcomes that are influenced by 9- to 12-month neurodevelopmental status and social disadvantage. By combining strategies to lessen biological risks and enhance developmentally appropriate environments, long-term outcomes of preschool children can be optimized.