The Best Pharmaceuticals for Children Act (BPCA; Pub L 107-109) was enacted in January 2002 and will sunset in October 2007. The BPCA established processes for studying off-patent and on-patent drugs that are used in pediatric population. Although some drugs have been successfully developed for the neonate (eg, surfactant, nitric oxide), drug development for the youngest, least mature, and most vulnerable pediatric patients is generally lacking. Most drugs are empirically administered to newborns once efficacy has been demonstrated in adults and usefulness is suspected or demonstrated in the older pediatric population. Unfortunately, this process undermines the ability to perform the appropriate studies necessary to demonstrate a drug's short- and long-term safety and efficacy and establish appropriate dosing in neonates. The Newborn Drug Development Initiative Workshop I (held March 29-30, 2004) specifically addressed scientific, clinical, and ethical concerns in the development of trials of pediatric therapeutic agents for neonates. Implementation of the BPCA for all pediatric populations will foster collaboration among federal agencies and academic institutions on scientific investigation, clinical-study design, and consideration of the weight of evidence and address ethical issues related to the performance of drug studies.