Unprecedented attention is focused on global health, with a four-fold increase in development assistance in the last 15 years and the scope of global health expanding beyond infectious disease to include chronic disease and health systems strengthening. As the global impact of health is more widely understood, it has become a crucial element of international relations, economic development, and foreign affairs. At this potential leverage point in the global health movement, the application of grand strategy is of critical importance. Grand strategy, i.e., the development and implementation of comprehensive plans of action to achieve large ends with limited means, has been refined through centuries of international relations and the management of states but has been inadequately applied to global health policy and implementation. We review key principles of grand strategy and demonstrate their applicability to a central global health issue: maternal mortality. The principles include: start with the end in mind, take an ecological approach, recognize that tactics matter, use positive deviance to characterize practical solutions and foster scale-up, and integrate timely intelligence and data into health interventions and improvement efforts. We advocate for the greater use of grand strategy in global health.