Introduction: The Abecedarian Project was a randomized controlled trial (RCT) that tested the effects of 5 years of early education combined with social and health supports on learning and cognitive development in infants from high-risk environments. This article provides a reflective review of its key findings from 50 years along with results from variations also tested in RCTs. Methods: The Abecedarian Project and its replications all used a comparative efficacy RCT design. The Early Education treatment group received systematic early education with pediatric health care, early nutritional enhancement, and family social services while the Health/Social Services comparison group received health and family supports but not the formal early education program. In childhood, key outcomes were cognition and school-age academic achievement; in adulthood, assessments included post-high school educational attainment, employment, income/assets, adult family relationships, brain development, and social decision-making. Results: At all tested ages after 12 months of age, the Abecedarian Early Education was associated with significant benefits in children’s cognitive development, school and educational achievements, and multiple indicators of positive health and indicators of adult social adjustment. Collectively, the major replication studies provide affirmation of the positive impact of high-quality early education, although the breadth and magnitude of benefits vary with the child’s environmental risks and dosage of the early education intervention. Some unexpected long-term associations include enhanced caring and future planning in social decision-making, positive relationships with parents, altered brain structure, and improved cardiovascular health. Conclusions: This series of RCTs improved developmental trajectories of infants born into multi-risk social, economic, and biological life circumstances, thus strongly resolving that human malleability is achievable. The challenge ahead concerns how to effectively disseminate and practically use these findings to realize widespread benefits. We nominate both a guiding conceptual framework to help plan and measure strategic interventions as well as a set of hallmarks associated with successful community implementation of effective child and family programs. (author abstract)