The International Health Regulations (2005) [IHR(2005)] represent a potentially revolutionary change in global health governance. The use of the regulations by the World Health Organization (WHO) to respond to the outbreak of pandemic influenza A 2009-H1N1 highlights the importance of the regulations to protecting global health security. As the 2009-H1N1 pandemic illustrated, the IHR(2005) have provided a more robust framework for responding to public health emergencies of international concern (PHEICs), through requiring reporting of serious disease events, strengthening how countries and WHO communicate concerning health threats, empowering the WHO Director-General to declare the existence of PHEICs and to issue temporary recommendations for responding to them, and requiring countries not to implement measures that unnecessarily restrict trade and travel or infringe on human rights. However, limitations to the effectiveness of the IHR(2005) revealed in the 2009-H1N1 pandemic include continuing inadequacies in surveillance and response capacities within some countries, violations of IHR(2005) rules and a potentially narrowing scope of application only to influenza-like pandemic events. These limitations could undermine the IHR(2005)'s potential to contribute to national and global efforts to detect and mitigate future public health emergencies. Support for the IHR(2005) should be broadened and deepened to improve their utility as a tool to strengthen global health security.