The goal of newborn screening is to identify medical conditions that can cause significant morbidity and/or mortality if not treated early in life. Pediatricians often play a vital role in the initial disclosure of newborn screening results and coordination of confirmatory testing, treatment, and referral to specialty care. The goal of this article is to provide an overview of current newborn screening in the United States, focusing on the various disorders, their manifestations, the newborn screening process, the confirmatory testing, and treatments. Some practical considerations will be discussed as well.