This paper identifies some of the more important diseases at the wildlife–livestock interface and the role wildlife plays in disease transmission. Domestic livestock, wildlife and humans share many similar pathogens. Pathogens of wild or domestic animal origin that can cause infections in humans are known as zoonotic organisms and the converse are termed as anthroponotic organisms. Seventy-seven percent of livestock pathogens and 91% of domestic carnivore pathogens are known to infect multiple hosts, including wildlife. Understanding this group of pathogens is critical to public health safety, because they infect a wide range of hosts and are most likely to emerge as novel causes of infection in humans and domestic animals. Diseases at the wildlife–livestock interface, particularly those that are zoonotic, must be an area of focus for public health programs and surveillance for emerging infectious diseases. Additionally, understanding wildlife and their role is a vital part of understanding the epidemiology and ecology of diseases. To do this, a multi-faceted approach combining capacity building and training, wildlife disease surveillance, wildlife–livestock interface and disease ecology studies, data and information sharing and outbreak investigation are needed.