The One Health High-Level Expert Panel’s definition of One Health includes optimizing the health of people, animals (wild and domestic) and ecosystems. For many One Health practitioners, wildlife that can spread zoonoses are the focus, particularly if they can come in contact with people. However, ecosystem health is often best-indicated by less-encountered species, for instance, amphibians and reptiles. This review highlights how these taxa can benefit human health and well-being, including cultural significance, as well as their impact on plant, animal and environmental health. We highlight current challenges to the health of these species and the need to include them in the One Health Joint Action Plan. We conclude with a call to action for inclusion of amphibians and reptiles in a One Health approach.