We have made important progress toward achieving Millennium Development Goals 4 and 5, with an estimated 47% decrease in maternal deaths and 28% decrease in newborn deaths globally since 1990. However, rapidly accelerating this progress is vital because far too many maternal and newborn deaths still occur each day. Fortunately, there are major initiatives underway to enhance global efforts in preventing these deaths, including the United Nations Secretary General's Global Strategy for Women's and Children's Health. We know why maternal and newborn deaths occur, where they occur, and how they occur, and we have highly effective interventions for preventing them. Nearly all (99%) maternal and newborn deaths occur in developing countries where the implementation of life-saving interventions has been a major challenge. Determining how best to meet this challenge will require more intensive interrelated efforts that include not only science-driven guidance on effective interventions, but also strategies and plans for implementing these interventions. Implementation science, defined as “the study of methods to promote the integration of research findings and evidence into healthcare policy and practice,” will be key as will innovations in both technologies and implementation processes. We will need to develop conceptual and operational frameworks that link innovation and implementation science to implementation challenges for the Global Strategy. Likewise, we will need to expand and strengthen close cooperation between those with responsibilities for implementation and those with responsibilities for developing and supporting science-driven interventions. Realizing the potential for the Global Strategy will require commitment, coordination, collaboration, and communication—and the women and newborns we serve deserve no less.