Newborn Dried Blood Spot Screening (NBS) is a core public health service and is the largest application of genetic testing in the United States. NBS is conducted by state public health departments to identify infants with certain genetic, metabolic, and endocrine disorders. Screening is performed in the first few days of life through blood testing. Several drops of blood are taken from the baby's heel and placed on a filter paper card. The dried blood, on the filter cards, is sent from the newborn nursery to the state health department laboratory, or a commercial partner, where the blood is analyzed. Scientific and technological advances have lead to a significant expansion in the number of tests—from an average of 6 to more than 50—and there is a national trend to further expand the NBS program. This rapid expansion has created significant ethical, legal, and social challenges for the health care system and opportunity for scholarly inquiry to address these issues. The purpose of this chapter is to provide an overview of the NBS programs and to provide an in-depth examination of two significant concerns raised from expanded newborn screening, specifically false-positives and lack of information for parents. Implications for nursing research in managing these ethical dilemmas are discussed.