The opioid crisis has grown to affect pregnant women and infants across the United States, as evidenced by rising rates of opioid use disorder among pregnant women and neonatal opioid withdrawal syndrome among infants. Across the country, pregnant women lack access to evidence-based therapies, including medications for opioid use disorder, and infants with opioid exposure frequently receive variable care. In addition, public systems, such as child welfare and early intervention, are increasingly stretched by increasing numbers of children affected by the crisis. Systematic, enduring, coordinated, and holistic approaches are needed to improve care for the mother-infant dyad. In this statement, we provide an overview of the effect of the opioid crisis on the mother-infant dyad and provide recommendations for management of the infant with opioid exposure, including clinical presentation, assessment, treatment, and discharge.