Global efforts to eliminate measles and rubella can be combined with other actions to accelerate the strengthening of health systems in developing countries. However, there are several challenges standing in the way of successfully combining measles and rubella vaccination campaigns with health systems strengthening. Those challenges include the following: achieving universal vaccine coverage while integrating the initiative with other primary care strategies and developing the necessary health system resilience to confront emergencies, ensuring epidemiological and laboratory surveillance of vaccine-preventable diseases, developing the human resources needed to effectively manage and implement national strategies, increasing community demand for health services, and obtaining long-term political support. We describe lessons learned from the successful elimination of measles and rubella in the Americas and elsewhere that strive to strengthen national health systems to both improve vaccine uptake and confront emerging threats. The elimination of measles and rubella provides opportunities for nations to strengthen health systems and thus to both reduce inequities and ensure national health security.