Neonatal abstinence syndrome from opioids (NAS-O) is a multisystem disorder resulting in neurological and gastrointestinal symptoms from the abrupt discontinuation of chronic fetal exposure to opioids. Increasing opioid use during pregnancy has led to a five-fold increase in NAS-O nationally over the past decade. Several knowledge gaps in our experiences with opioid-exposed neonates have been identified: 1) universal maternal screening; 2) diagnostic tools for newborn abstinence syndrome; 3) optimal treatment protocols; and 4) long-term neurodevelopmental effects of fetal opioid exposure. This review article gives a broad overview of the issues associated with screening, diagnosis, and management of opioid exposure in newborns as well as the issues with collecting accurate outcomes data to monitor efforts aimed at curbing opioid exposure in children and NAS-O. Data specific to Oklahoma is provided, when available.