Opioid dependent pregnant and postpartum women and their infants are a complex and vulnerable population requiring individualized, comprehensive, and multidisciplinary treatment. Though methadone maintenance in the setting of comprehensive service provision during pregnancy significantly improves pregnancy outcomes for opioid dependent women, its use has implications for the infant, most notably the neonatal abstinence syndrome. Neonatal abstinence syndrome is comprised of physiologic signs and behaviors that indicate a dysfunctional regulation of the central and autonomic nervous systems, and is variable in its expression in affected infants. The disorganized rather than adaptive behaviors displayed by each infant undergoing the effects of in utero opioid exposure may impair basic functions such as feeding, sleeping, and the ability to be alert and communicate clear cues to caregivers. Understanding and responding to neurobehavioral dysfunction of the newborn may help to promote the infant’s self-organization and self-regulating abilities. However, the substance abusing mother’s physical and psychologic wellbeing may be debilitated in the perinatal period, and her ability to recognize and respond to the newborn’s cues may be limited. A multitiered comprehensive assessment and intervention of the methadone-maintained mother, her child, and the mother/infant dyad can improve early maternal nurturing interactions, a crucial component of early infant development, particularly in this vulnerable population. The purpose of this article is to review the contribution of maternal opioid dependency to the difficulties experienced by the mother-infant dyad and their treatment providers in the postnatal period, and the nonpharmacologic treatment of the infants with suggestions for practical measures with emphasis on the treatment of the mother and baby as an interactional dyad.