As its name suggestes, Global Health aims to approach health issues broadly and comprehensively both from a geographical and a conceptual point of view. In this demand, the human–animal–ecosystem interface cannot be left behind: the One Health approach, an improved integration among disciplines that enhances cross-sectoral collaboration between stakeholders at different levels, is paramount. It increases public health efficiency and effectiveness through a better understanding of diseases and risk factors through shared efforts that will benefit human, animal, and ecosystem health. Successful results were already achived in key global health issues, such as zoonotic diseases, antimicrobial resistance, and food safety but a lot remains to be done. The integration that led to these promising outcomes was not spontaneously achieved, but it was structured through methodological principles, guidelines, and related transaction costs. However, the procedural shift is a highly rewording effort that have multiple but still unattempt field of application.