Both early intervention (EI) programs for infants and toddlers with disabilities and newborn screening (NBS) programs to identify specific disorders shortly after birth rest on the assumption that the best way to prevent or lessen the impact of a disorder is to provide treatment as early as possible. Despite this shared vision, the two programs differ in substantial ways, including historical beginnings and subsequent evolution; program entry and eligibility; service models; evidence, efficacy, and outcomes; roles and responsibilities vis-à-vis families; and financing. Each program is well established and highly successful. But 4 crosscutting issues need to be addressed: (1) documenting meaningful outcomes for children and families; (2) deciding whether and how to provide highly effective yet very expensive treatments; (3) implementing surveillance activities to monitor progress and determine optimal timing for intervention; and (4) identifying appropriate intersections between EI and NBS. Solving these challenges will require national and state leadership, stakeholder engagement, collaboration between EI and NBS, and a significant investment of resources if the promise of maximizing benefit for children and families is to be realized.