How can families in the most difficult circumstances be supported to give children the best chance to succeed? Federal administrators of the Early Head Start program for young children and families think addressing the sources of toxic stress [1] may be the answer. Recognizing the potential benefits to society—and potential improvements in outcomes for the families they serve—the U.S. Administration for Children and Families (ACF) [2] has launched a trailblazing research effort to find more effective ways to enhance child development in the nation’s poorest families.