Over the last 15 years neonatal morbidity and mortality have changed little for very low birth weight (VLBW) babies despite significant technological and therapeutic advances. While clinical trials and animal models have until recently improved outcomes in this gestational age group, further productivity from these traditional sources are not likely. A recent study of monozygotic and dizygotic twins shows that the main determinants of neonatal morbidity and mortality in VLBW babies--bronchopulmonary dysplasia, necrotizing enterocolitis, and intraventricular hemorrhage--have significant genetic components. Incremental improvements in the future, therefore, will likely depend on identification of these genetic components for targeting specific therapies. Cost-effective methods and resources, fueled by the Human Genome and HapMap Projects and recent successes in identifying genes for a small number of complex genetic diseases, are available now and through creative planning and timely implementation would likely yield useful results.