Ontario's clinical practice guidelines for neonatal abstinence syndrome (NAS) provide evidence-informed recommendations that address the needs of substance using pregnant women and newborns at risk of NAS. NAS is a complex and multifaceted issue that is escalating along with rapidly rising opioid use in Ontario. Reducing the incidence and impact of NAS requires immediate action in order to improve the care of affected women and infants. This includes optimizing and standardizing treatment strategies, assessing and managing social risk, better monitoring of prescribing practices and facilitating the implementation of better treatment and prevention strategies as they become available. These clinical practice guidelines provide the framework to inform and support the development of a coordinated strategy to address this important issue and to promote safe and effective care.