In our rapidly changing world, there is an increasing need for creative local and global solutions to health challenges impacting people, animals, and ecosystems. While a primary focus has been infectious diseases shared by people and animals (zoonotic diseases such as Ebola, Rabies, and Avian Influenza), the One Health approach can be applied to many health issues at the human-animal-environment interface including antimicrobial resistance, non-infectious diseases, food safety and nutrition, and water quality. Although humans are impacted by zoonotic and other diseases, our impacts on the environment through land use, animal management, and climate change also play a key role in shaping health. In Rwanda and Nebraska, where many people are dependent upon the local environment for agricultural livelihoods and human-animal contact is common, a One Health approach is critical to understand and address health challenges impacting humans, domestic and wild animals, and their shared environments. Our aim is to create a long-term, collaborative One Health framework linking partners in Rwanda and Nebraska to facilitate One Health research, training, capacity building, and outreach.