Yellow fever is a viral zoonosis of variable geographic distribution in the Americas. With no specific treatment for this vector-borne disease, vaccination is the best prevention available. This flavivirus has been circulating in the Americas since the late 15th century, and over the past decades, the virus has reemerged and is now endemic in 13 countries in South and Central America. Ecosystem changes may have had a role in this reemergence. The International Health Regulations were approved by the World Health Assembly in 2005 as a guidance document to support national policies with important measures for disease control and prevention of new epidemics. This article presents an illustrative case of the efforts of three ministries of health in the Americas (Dominican Republic, Ecuador, and Honduras) to implement international guidelines and reduce yellow fever transmission in the region. Using the One Health framework, we propose selected recommendations for the prevention and control of yellow fever outbreaks.