Safety culture, an aspect of organizational culture, that reflects work place norms toward safety, is foundational to high-quality care. Improvements in safety culture are associated with improved operational and clinical outcomes. In the neonatal intensive care unit (NICU), where fragile infants receive complex, coordinated care over prolonged time periods, it is critically important that unit norms reflect the high priority placed on safety. Changing the safety culture of the NICU involves a systematic process of measurement, identifying strengths and weaknesses, deploying targeted interventions, and learning from the results, to set the stage for an iterative process of improvement. Successful change efforts require: effective partnerships with key stakeholders including management, clinicians, staff, and families; using data to make the case for improvement; and leadership actions that motivate change, channel resources, and support active problem- solving. Sustainable change requires buy-in from NICU staff and management, resources, and long-term institutional commitment.