Newborn screening is a major public health achievement, enabling early detection and treatment of serious medical conditions before onset of irreversible damage to health. The scope of newborn screening has continuously expanded with the addition and innovations in screening platforms including tandem mass spectrometry. Genomic newborn screening provides another platform using genomic DNA sequencing as a first-tier test to improve and expand screening for actionable genetic conditions. Genome coverage affords flexibility to incorporate new diseases rapidly as new effective therapies are available.