The cold and arid mountains and plateaus of High Asia, inhabited by a relatively sparse human population, a high density of livestock, and wildlife such as the iconic snow leopard Panthera uncia, are usually considered low risk for disease outbreaks. However, based on current knowledge about drivers of disease emergence, we show that High Asia is rapidly developing conditions that favor increased emergence of infectious diseases and zoonoses. This is because of the existing prevalence of potentially serious pathogens in the system; intensifying environmental degradation; rapid changes in local ecological, socio-ecological, and socio-economic factors; and global risk intensifiers such as climate change and globalization. To better understand and manage the risks posed by diseases to humans, livestock, and wildlife, there is an urgent need for establishing a disease surveillance system and improving human and animal health care. Public health must be integrated with conservation programs, more ecologically sustainable development efforts and long-term disease surveillance.