Emerging infectious disease threatens amphibian biodiversity worldwide, including in landscapes that are protected from many anthropogenic stressors. We summarized data from studies in the Greater Yellowstone Ecosystem (GYE), one of the largest and most complete temperate-zone ecosystems on Earth, to assess the current state of knowledge about ranaviruses and the novel amphibian chytrid fungus (Bd) in this landscape, and to provide insight into future threats and conservation strategies. Our comprehension of these amphibian diseases in the GYE is based on >20 years of monitoring, surveys, population studies, and opportunistic observations of mortality events. Research indicates that local species are affected differently, depending on temperature, community structure, and location in the GYE. Bd has not been linked to die-offs in the GYE but evidence for ongoing reductions in survival contributes to foundational data about the effects of this pathogen in North America. Localized mortality events attributed to, or consistent with, disease from ranaviruses, are widespread in the GYE, but there is less information on how ranaviruses affect amphibian vital rates. The significance of disease in the long-term persistence of amphibians in the GYE is linked to anticipated changes in climate, especially drought. Additionally, expected increases in visitor use, and its associated impacts, have the potential to exacerbate the effects of disease. Long-term information from this large, intact landscape helps to frame our understanding of the effects of disease on amphibians and provides data that can contribute to management decisions, mitigation strategies, and forecasting efforts.