The COVID-19 crisis brought home the high costs of pandemics, triggering a historic setback in the fight against poverty. It also reinforced the interconnections between people, planet and economy, calling attention to the zoonotic nature of pathogens spilling over from animals to people. To decrease their burden, we must focus on prevention. The One Health approach proposes a way forward to reduce risk of spillover. Recognizing that the health and well-being of humans, animals, and their shared ecosystems are interdependent, One Health is designed as an integrated, practical, multisectoral framework for pandemic prevention. By stopping infectious diseases from spilling over to people and spreading to become pandemics, One Health provides a solid foundation for global health security and improved development outcomes at much lower societal and economic costs. This report aims to shed light on the benefits of prevention to serve as a wake-up call for policymakers and finance ministers alike. The report also outlines an investment framework and One Health architecture for zoonotic disease prevention. As you will read on these pages, compared to the sky-high cost of bringing pandemics under control, relatively modest investments in prevention will pay huge dividends.