In this article, we examine the status of the National Institutes of Health (NIH) pediatric research portfolio between start of federal fiscal year (FY) 1992 and end of FY 2015. The NIH experienced the greatest mean annual growth rate during the “doubling era” (FY 1998-2003): both the NIH budget (13.5%) and pediatric research portfolios (11.5%) increased annually by double digits. However, in the “postdoubling” era (FY 2004-2009), both the NIH (2.0%) and pediatric (−0.2%) mean annual growth rates decreased dramatically. In the most recent era (FY 2010-2015), the NIH mean annual growth rate has been flat (−0.1%) and pediatric research funding has posted very modest gains (3.5%) without accounting for 1-time increases under the 2009 American Recovery and Reinvestment Act. We offer recommendations to protect against further erosion of the pediatric research portfolio because continuation of these trends will have a negative effect on the health of children during their childhood and as adults. As capacity to conduct basic and applied research is further constrained, it will be a challenge for pediatric researchers to do more with less and less.