The Ethiopian wolf (Canis simensis) is the rarest canid in the world, with half a dozen surviving populations at constant risk from dog-related diseases, such as rabies and canine distemper virus. Intensive vaccination of neighbouring domestic dogs in the Bale Mountains has proved insufficient to fully prevent these viruses from spilling over into the wolf population, due to the large numbers of sympatric dogs and their high turnover. Where outbreaks have been detected in the wolves, responsive parenteral vaccination has been the key disease management approach. A new strategy for an integrated disease management is urgently required to protect the wolves, and also achieve ‘one health’ spill-over benefits to humans, livestock, dogs and other wild carnivores. We describe mortality patterns and analyse long-term demographic data to disclose the crucial role of pack formation in wolf population recovery. We assess the spatial and temporal dynamics of viral pathogens, their transmission from reservoir free-ranging dog populations to wildlife, and consider the effectiveness of preventive oral vaccinations. Using simulation models to test alternative disease management strategies we present some recommendations for the future management of disease in Ethiopian wolf populations.