As advances are made in understanding the human genome, newborn screening for a variety of different diseases becomes more prevalent. Although this screening can provide a number of benefits, it also may be associated with various negative psychosocial consequences, including heightened uncertainty and anxiety about the child's health. Relying on videotaped interactions between health care providers and families whose child received a positive newborn screening test for cystic fibrosis (CF; N = 17), in this article we report on how the respective parties manage uncertainty. Although the goal of the providers appears to be one of reducing uncertainty, all parties to the interaction engage in behaviors that both manage and negotiate as opposed to just reduce uncertainty. Implications for theorizing about uncertainty management are discussed.