Abstract This longitudinal, descriptive study gathered information on drug-exposed infants at home and identified effective public health nurse interventions for them and their caregivers. These infants exhibit symptoms that may well interfere with their ability to give clear cues as part of the infant-care-giver interactive system. This may amplify or perpetuate the effects of the drugs and low birth weight. Fifteen infants with a positive toxicology screen were compared to controls at birth and followed for up to 12 months of age through home visits by a public health nurse practitioner. The drug-exposed infants were significantly smaller at birth, and their most common initial problems were the need for nonnutritive sucking, excessive extensor tone, infections, and irritability. The mean weight, length, and head circumference went from the 10th to the 25th percentile at birth to the 25th to 50th percentile at 12 months. The support system and organization of the home predicted the family's ability to sustain caregiving for these infants. Effective strategies to care for these infants included recognizing states and cues, swaddling, use of pacifier, waking to eat, and smaller feedings. The role of the public health nurse was crucial for conducting early assessment, implementing strategies, and facilitating a therapeutic relationship.