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The current review provides an update focused on the evolving epidemiology of neonatal abstinence syndrome (NAS), factors influencing disease expression, advances in clinical assessment of withdrawal, novel approaches to NAS treatment, and the emerging role of quality improvement in assessment and management of NAS.The rise in the incidence of NAS disproportionately occurred in rural and suburban areas. Polysubstance exposure and genetic polymorphisms have been shown to modify NAS expression and severity. New bedside assessments using a limited number of factors to identify infants with NAS result in fewer infants receiving pharmacotherapy. In addition, buprenorphine may be a promising therapeutic alternative to morphine to treat NAS. Lastly, local, state, and national quality improvement initiatives have emerged as an effective mechanism to advance the care of infants with NAS.NAS remains a critical public health issue associated with significant medical, economic, and personal burdens. Emerging data on associated risk factors, assessment of and treatment for NAS provide clinicians and hospitals with new knowledge and an urgency to promote standardization of care for infants with NAS.