The management of the infant exposed to drugs in utero poses significant challenges. Symptoms and signs of neonatal abstinence syndrome (NAS) are non-specific but most commonly associated with withdrawal from maternal opioids. A high index of suspicion is required when presented with an infant who could be manifesting symptoms of NAS. In the absence of a reliable history of maternal drug exposure, analysis of neonatal meconium or urine may be indicated. Approximately 90% of infants exposed to opioids will exhibit signs of NAS, although a smaller proportion will require pharmacological treatment. Although few studies have evaluated the advantages of different therapeutic agents and strategies, opioid withdrawal is best treated initially with opioid medication. Supportive care of the infant should include assessment of the adequacy of feeding, evaluation of social circumstances (particularly child protection issues) and surveillance for transmission of viral infection.