Dogs are the source of more than 99% of human rabies virus infections in endemic regions. Without postexposure prophylaxis, almost all cases are fatal, making rabies the most lethal infectious disease. Tens of thousands of deaths are reported annually, but the official figures are believed to be gross underestimates. Controlling canine rabies, especially in free-ranging dogs, is the first priority to reduce the burden of human disease. Because of their limited medical infrastructure, most endemic countries lack the laboratory facilities needed to diagnose human cases of viral encephalitis. Moreover, the veterinary sectors are often unable to undertake systematic surveillance and reporting of rabies in animals. Without an adequate and functioning risk assessment system that is primed for use, rabies will remain a ‘neglected’ and omnipresent disease, especially in poverty-stricken regions of the world. Fortunately, experience with the elimination of canine rabies from many industrialized countries has shown that these barriers are not insurmountable. Successful rabies prevention and control strategies that prove the absence of the disease depend on laboratory-based surveillance, rapid data reporting and an adequate system of risk assessment. Future control and prevention programmes should therefore coordinate the development of these key factors, creating synergies to eliminate rabies at its animal source. This article forms part of a symposium in Antiviral Research on the global elimination of canine rabies.