Disease ecology aims at studying host-pathogen interactions in the context of their environment and evolution. It is concerned with how species interactions and abiotic components of the environment affect patterns and processes of infectious diseases. As such, this emerging discipline is highly relevant to improve our understanding and management of diverse and complex wildlife-livestock interfaces across the globe. We illustrate with various examples how the processes of pathogen transmission among interacting wild and domestic host populations may be analysed using tools and concepts drawn from population, landscape and evolutionary ecology. In particular, we emphasise the importance of access to resources, interspecific competition and predation in shaping the frequency and intensity of direct and indirect contacts among potential hosts at the interface. Moreover, we report on the growing importance of anthropogenic factors shaping wildlife-livestock-human interfaces, with recent changes in both livestock husbandry and biodiversity conservation practices having major impacts on pathogen emergence and spread in interface areas. We conclude by laying out the importance of the interdisciplinary integration of ecological, bio-medical and social sciences into a single discipline of “disease socio-ecology”, which remains a major research frontier for improved management of wildlife-livestock interfaces.