Natural ecosystems are facing unprecedented threats which directly threaten human well-being through decreases in critical ecosystem services (IPBES 2019). The top five drivers causing the largest global impacts to biodiversity and ecosystem services include: 1) changes in land and sea use; 2) direct exploitation of organisms; 3) climate change; 4) pollution, and 5) invasive alien species (IPBES 2019). Although One Health acknowledges the link between the health of humans, animals, and the environment, One Health discussions have historically focused on the prevention and control of infectious disease at the human-animal interface rather than these large-scale drivers of health. While One Health has succeeded in bringing awareness to the need for proactive disease control measures such as strengthened biosecurity and vaccine development (e.g., Machalaba et al., 2018; Middleton et al., 2014), disease is only one component of health. In this chapter, we explore the potential for One Health to shift its focus from disease prevention to health promotion to more fully integrate solutions that protect the health of humans, animals, and the ecosystems on which we all depend for our economies, livelihoods, food security, and health. This shift will facilitate a more seamless inclusion of ecological health and environmental conservation in the One Health paradigm and can serve as the basis for a comprehensive approach to complex problems at the root of global health. We also suggest a framework for creating and applying health metrics for wildlife and ecological systems that will be essential for measuring the success of actions aimed at maintaining or shifting systems to desired states.