The Global Response to Avian Influenza was initially established under the joint leadership of the European Union, the United States and the United Nations System Influenza Coordination Office. Since then it has supported numerous initiatives, including the World Health Organization (WHO)/Food and Agriculture Organization of the United Nations (FAO)/World Organisation for Animal Health (OIE) Global Early Warning System (GLEWS). Indeed, the Global Response to Avian Influenza paved the way for an unprecedented WHO/FAO/OIE tripartite partnership, which promoted the integration of foodborne, neglected zoonotic and tropical diseases within the One Health movement and led to the tripartite High-Level Technical Meeting of 2011 in Mexico. The One Health Global Network, which began as a proposition at an Expert Consultation in Winnipeg, Canada, in 2009, is now a reality. While its Global Guidance Group takes shape, the choice of soft governance – an approach which relies more on information and advisory guidelines than on hierarchy and legislation, and which aims to steer local organisations rather than to control them – remains challenging. Nonetheless, the emergence of One Health as a professional and academic discipline, together with the growing references to a One Health culture, also offers new opportunities.