In the 19th century, a theory existed that infants born to opioid dependent pregnant women were unaffected because morphine use among women was associated with sterility and a loss of sexual desire. Currently, it is well known that maternal drug dependence is associated with a number of complications, including NAS that may affect the fetus. The existing questions are what have we learned from past practices, what are the recent findings and where should we go from here with regard to NAS? Signs of neonatal abstinence have classically been divided into four major systems: central nervous, gastrointestinal, respiratory, and the autonomic nervous system. The appropriate treatment of neonatal opioid abstinence is based on the principles of accurate diagnosis and assessment. Therapy is aimed at rapid clinical stabilization of the opioid-exposed baby followed by gradual reduction of medication, if required, under careful medical supervision. A great deal has been learned over the past 5 decades as to what factors may influence the severity of clinical expression of NAS. If maternal withdrawal equates with fetal withdrawal, can maternal withdrawal, or under-dosing, or even single dosing during treatment sensitize the fetus to withdrawal or otherwise compromise fetal health, i.e. stress the fetus during development? Neonatal Abstinence Syndrome is a complex diagnosis, but understanding it and using sound principles makes it easy for the baby and the treating medical professionals. The baby with NAS has gone a long way from no recommended assessment and treatment and no plausible hypotheses regarding mechanisms to improved research and clinical practices. The next phase of research will bring the baby with NAS to the 21st Century and beyond!