Neonatal abstinence syndrome refers to the signs and symptoms attributed to the cessation of prenatal exposure (via placental transfer) to various substances. This Primer focuses on neonatal abstinence syndrome caused by opioid use during pregnancy - neonatal opioid withdrawal syndrome (NOWS). As the global prevalence of opioid use has alarmingly increased, so has the incidence of NOWS. NOWS can manifest with varying severity or not at all, for unknown reasons, but is likely to be associated with multiple factors, both maternal (for example, smoking and additional substance exposures) and neonatal (gestational age, sex and genetics). Care for the infant with NOWS begins with addressing the issues experienced by pregnant women with opioid use disorder. Co-occurring mental illness, economic hardship, intimate partner violence, infectious diseases and limited access to care are common in these women and can result in poor maternal and neonatal outcomes. Although there is no consensus regarding optimal NOWS management, non-pharmacological interventions (such as breastfeeding and rooming-in of the mother and the baby) have become a priority, as they can ameliorate symptoms without the need for further opioid exposure. Untreated NOWS can be associated with morbidity in early infancy, and the long-term consequences of fetal opioid exposure are only beginning to be understood.