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Over the last 15 years the prevalence of neonatal abstinence syndrome (NAS) increased almost five-fold. A considerable diversity seems to prevail in the management of NAS. This review provides an overview of factors affecting the expression and course of NAS, and recent developments in NAS assessment and treatment.Apart from different pharmacological and nonpharmacological treatment modalities, maturity of the infant and genetic variations likely are (co)responsible for interpatient variability in NAS severity, despite similar maternal exposure. Recent efforts concerning the further development of NAS severity scoring systems focus on the development of brief screening measures; in addition, pupil diameter and skin conductance have been proposed as complements to observer-rated scales. The decrease in incidence of NAS begins in the appropriate management of medication assisted treatment of the mother.Mitigating the negative outcomes for infants affected by NAS, their mothers and the healthcare system implies, first and foremost, developing and implementing an organized protocol for the management of NAS, and the homogenous use of a standardized scoring system utilizing interobserver reliability and a guide for medication initiation, maintenance, and weaning which is consistent with traditional methods of treatment for neonates.