In the past two decades, the concept of “One Health” has emerged as a compelling framework for improving the health of people, animals, plants and ecosystems. Despite its growing popularity, One Health should not be seen as a silver bullet solution to all health challenges, as many are not at the interface between sectors. What’s more, there have been serious difficulties translating One Health from ideas into practice, and many barriers still exist to operationalizing the concept effectively. Nonetheless, the One Health concept continues to gather significant momentum across the globe. This explainer introduces the concept of One Health. It covers the key ideas, origins, actors and debates, outlining One Health’s advantages relative to sectoral approaches to tackling today’s health threats. The cases at the end of the explainer provide additional examples of the added value of taking a One Health approach to address some of today’s most pressing health issues.