The absence of responsive relationships poses a serious threat to a child’s development and well-being. Sensing threat activates biological stress response systems, and excessive activation of those systems can have a toxic effect on developing brain circuitry. When the lack of responsiveness persists, the adverse effects of toxic stress can compound the lost opportunities for development associated with limited or ineffective interaction. This complex impact of neglect on the developing brain underscores why it is so harmful in the earliest years of life. It also demonstrates why effective early interventions are likely to pay significant dividends in better long-term outcomes in educational achievement, lifelong health, and successful parenting of the next generation.