In the United States, many health care systems function independently from one another. Increasing coordination across systems has the potential to vastly improve services and patient outcomes, yet implementing these changes can be challenging, requiring increased communication, interaction, and coordination across systems that typically function independently. Parental depression is one health issue that could benefit greatly from a comprehensive systems approach. The Helping Families Raise Healthy Children initiative is a cross-system quality improvement initiative aimed at improving identification and treatment of families faced with the dual challenge of caregiver depression and early childhood developmental delays. Four main techniques were used to foster and sustain cross-system collaboration and communication: cross-system trainings, regular meetings of collaborative partners, a cross-system learning collaborative for service providers, and two cross-system facilitators. The initiative achieved successful cross-system collaboration, suggesting that these methods may be used in other initiatives to foster similar types of collaboration across systems.