The National Children's Study (NCS) is a national longitudinal study that will prospectively investigate the influence of biological, environmental, genetic, and social factors on the health and development of US children. The NCS was mandated by the Children's Health Act of 2000 (Public Law 106-310) and is being implemented by the National Institutes of Health with input from the Centers for Disease Control and Prevention (CDC), the Environmental Protection Agency, and other federal departments and agencies. The NCS is a data-driven, evidence-based, community- and participant-informed study. Given its scale and scope, the NCS is an integrated system using several data acquisition strategies intended to provide evidenced-based design of methodologies and protocols. These strategies include the Vanguard Study, the Main Study, and formative research and sub-studies. The Vanguard Study, a pilot study, is currently underway and has been expanded from 7 to 37 study locations. The original study protocols and recruitment strategy have been field tested and revisions are under consideration. The CDC is collaborating with NCS in a pilot study that evaluates biological specimen protocols and will provide results on a broad array of environmental chemical exposures and nutritional indicators for a sample of Vanguard Study participants. This study is an example of the kind of collaborative opportunity that would benefit the NCS. Medical toxicologists have unique training in basic and clinical toxicology and laboratory assessments, and by partnering with study centers, both the NCS design and future NCS research projects could be enhanced.