The maternal opioid epidemic has led to a substantial increase in the number of infants born with neonatal opioid withdrawal syndrome (NOWS). This chapter examines the immediate and long-term challenges faced by these infants and their families. Infants with NOWS present with a distinctive constellation of symptoms, including nervous system irritability, autonomic nervous system overactivity, and gastrointestinal dysregulation, resulting in an extended length of stay for the newborn hospitalization. The financial burden of caring for infants with NOWS has placed substantial strain on the US healthcare system, with annual costs escalating over the past two decades from tens of millions to more than half a billion dollars. These economic pressures, combined with clinical concerns about the treatment of infants and families affected by maternal opioid use, have driven recent innovation in the field. This chapter examines the evolution from the traditional Finnegan approach to the newer Eat, Sleep, Console model, which emphasizes family-centered care. Beyond the immediate postpartum period, research indicates that infants with NOWS face elevated risks for hospital readmission, particularly for neglect, failure to thrive, and traumatic injuries. The chapter concludes with recommendations for improved discharge planning, highlighting the need for standardized and integrated care models that address both the infant’s medical needs and the mother’s opioid use disorder.