Neonatal abstinence syndrome (NAS) is suffered by infants withdrawing from substances on which they have become physically dependent after in utero exposure. They may require prolonged treatment and spend weeks or even months in hospital. A wide range of drugs have been used to treat NAS. The efficacy of few, however, have been adequately investigated. Evidence suggests that opioids are the most appropriate, at least in infants exposed to diamorphine or methadone. In all “head to head” trials, diazepam has been shown to be ineffective. Morphine and methadone are currently the most commonly prescribed opioids to treat NAS, but randomised trials have not been undertaken to determine which is the more beneficial. Many infants with NAS have been exposed to multiple substances in utero. Further research is required into whether a single opiate or a multiple drug regimen is the best option for such patients.