One Health brings the powerful interrelationship between human and wildlife health together with ecosystem health. The initial concept of One Health was formulated decades ago and focused on disease transfer from wildlife to human populations. More recently, the concept has been used to associate resilience to disease with the health of the ecosystem and resilience to environmental stressors. The need for a One Health approach is particularly evident in the plight of Old World vultures, which are facing a conservation crisis due to drastic reductions in populations across their entire range. Moreover, vulture conservation exemplifies many contemporary tenets of One Health; vultures are critical to a sustainable and resilient ecosystem, which in turn is essential for the socio-ecological health of human communities. In this review, we examine the complex factors contributing to the demise of Old World vulture populations, using the lens of One Health to conceptualize the primary drivers impacting the health and sustainability of these populations. The One Health concept provides the basis for the development of a framework that incorporates a multidimensional approach and includes human health, wildlife health, environmental and disease-related stressors, disease incidences, societal pressures, and environmental contaminants. Integrating societal needs with management aimed at maintaining healthy vulture populations is key for successfully using a One Health framework to optimize the health of human and wildlife populations and ensure ecosystem health.