In the first half of the 20th century, rabies in dogs affected Canada, Mexico and the United States of America (USA). However, the role of wildlife in the transmission of the rabies virus was also recognised and outbreaks affecting both wildlife and domestic animals were documented. Canine rabies has since been eliminated from Canada and the USA, and is now only found sporadically in a few southern states of Mexico. Wildlife variant rabies viruses, found throughout the continent and geographically associated with specific reservoir species, have notable public and animal health, as well as economic, impacts. Early rabies control efforts included legislated dog management strategies and wildlife population reduction, which met with varying success. In the last 30 years, programmes for the control of rabies in dogs and wildlife have benefited from an 'Integrated Management Approach', combining education, vaccination (parenteral and oral), strategic population control, responsible pet ownership and effective stewardship of natural resources, in addition to cooperation and collaboration among local, national and international stakeholders. Looking ahead, the goal of eliminating specific wildlife virus variants will be challenged by the potential range expansion of reservoir species, due to climate change and other factors, and the risk of re-introducing eliminated virus variants. To be successful, programmes must be sustained and accompanied by advances in vaccines, enhanced distribution strategies, monitoring in the field and effective modelling of disease spread. They should also be informed by robust case surveillance, phylogenetics and an increased knowledge of vector ecology.