Background: The use of genome-wide (whole genome or exome) sequencing for population-based newborn screening presents an opportunity to detect and treat or prevent many more serious early-onset health conditions than is possible today. Methods: The Paediatric Task Team of the Global Alliance for Genomics and Health’s Regulatory and Ethics Working Group reviewed current understanding and concerns regarding the use of genomic technologies for population-based newborn screening and developed, by consensus, eight recommendations for clinicians, clinical laboratory scientists, and policy makers. Results: Before genome-wide sequencing can be implemented in newborn screening programs, its clinical utility and cost-effectiveness must be demonstrated, and the ability to distinguish disease-causing and benign variants of all genes screened must be established. In addition, each jurisdiction needs to resolve ethical and policy issues regarding the disclosure of incidental or secondary findings to families and ownership, appropriate storage and sharing of genomic data. Conclusion: The best interests of children should be the basis for all decisions regarding the implementation of genomic newborn screening.