Abstract: Over the last 50 years, routine newborn blood screening for congenital disorders has been hailed as a miracle of modern science, saving countless lives by providing a means to detect and treat life-threatening disorders before symptoms present. Despite progress made with more than 5,000 babies effectively identified with rare conditions each year, congenital anomalies collectively remain at the top of the list as the cause of death for babies under 1 year of age, accounting for more than 20% of all infant mortalities. Rapid technological advances have seen the original singular newborn screen for phenylketonuria expand to a core set of 34 conditions and an additional 26 secondary conditions on the Recommended Uniform Screening Panel, with wide state-to-state variation for implementation. As genomic analysis evolves to enable next-generation sequencing, debates continue over the ethical, legal, and social implications of identifying conditions for which there is no effective treatment. Nurse practitioners should be engaged and informed in providing evidence-based support to families engaging in ethical complex decision making surrounding newborn screening while effectively balancing risk-benefit analysis with individual beliefs and values.