The launch of the Global Health Security Agenda (GHSA) in February 2014 capped over a decade of global efforts to develop new approaches to emerging and reemerging infectious diseases-part of the growing recognition that disease events, whether natural, accidental, or intentional, threaten not just public health, but national, regional, and global security interests. In 2005, the United States, along with other Member States of the World Health Organization (WHO), adopted the revised International Health Regulations [IHR (2005)]. The IHR (2005) conferred new responsibilities on WHO and the global health community to coordinate resources for capacity building and emergency response, and on the now-196 States Parties to develop the core capacities required to detect, assess, report, and respond to potential public health emergencies of international concern. Both GHSA and the IHR aim to elevate political attention and encourage participation, coordination, and collaboration by multiple stakeholders, while leveraging previously existing commitments and multilateral efforts. GHSA and the IHR (2005) are platforms for action; how efforts under each will complement each other remains unclear. Mechanisms that measure progress under these 2 overlapping frameworks will aid in focusing resources and in sustaining political momentum for IHR implementation after 2016.