Africa is faced with many of the most daunting challenges of our time. It comprises roughly 15% of the world's human population, and most of its countries are perpetually ranked "Low" on the United Nations' Human Development Index. On the other hand, Africa has arguably the largest proportion of intact natural ecosystems, biodiversity, and sociocultural capital and the lowest impact on global warming of any continent. Thus, African leaders are faced with competing demands and values among a multitude of complex issues, such as high human population growth, extreme poverty, food insecurity, land use policy, climate change, and biodiversity conservation. In this context, building sustainable national systems for human and/or animal health is one of the grand challenges of this generation. Today's complex global health and development challenges require long-term commitment and a range of approaches that are too broad for any one discipline, institution, or country to implement on its own. The One Health concept recognizes the interconnectedness of global health issues and, as such, promotes the importance of and need for international, interdisciplinary, and cross-sectoral communication and collaboration at local, national, and international levels. By taking advantage of natural cultural tendencies for shared leadership, resource allocation, and community values, African leaders are currently proactively demonstrating the principles of One Health, and thus becoming a model for this global vision. And by focusing on partnerships rather than donor-recipient relationships, they are fostering the development of shared priorities and are increasingly driving their own health agenda to fulfill their own needs.