The objective of this study was to determine drug use in newborns at an inborn tertiary care neonatal intensive care unit, serving a predominantly African American population, to identify educational/research priorities in neonatal drug therapy. Data on demographics and exposure rates to all drugs from 6839 neonates born between January 1997 and June 2004 were analyzed. Number of drugs used was correlated with race, gender, gestational age, birthweight, and survival status. The contribution of these factors to mean drug use was predicted by multivariate regression analysis. In this population of 80% African Americans, mean drug use was 3.6/infant, with the highest use in the 24- to 27-week gestational age group (11.7/infant). Ampicillin and cefotaxime had the highest exposure rates. Premature infants had high use of surfactant, pressor agents, and diuretics. Caucasians, males, gestational age <28 weeks, and birthweight <1000 g were the risk factors for higher drug exposure. Future research/education must emphasize these therapeutic areas with priority assigned to low-birthweight infants.