Technical Abstract: With the exception of a systematic quarantine zone in south Texas along the border with Mexico, cattle fever ticks (CFT), i.e. Rhipicephalus (Boophilus) microplus and R. (B.) annulatus, were officially eradicated from the U.S. in 1943. Because of their roles as vectors of bovine babesiosis, the re-emergence of CFT is a real and imminent threat to the livestock industry. It is estimated that the livestock industry realizes annual savings totaling over 3 billion dollars at today’s currency rate since the U.S. was declared free of CFT and bovine babesiosis. The increased risk for bovine babesiosis in U.S. cattle associated with the apparent surge in CFT outbreaks observed since 2004 prompted a revision of the research agenda through a public workshop organized in 2009. Revised initiatives are underway to address knowledge gaps related to epidemiology and surveillance; ecology and biology of tick vectors and wildlife; diagnosis, treatment, and prevention; integrated approaches for CFT eradication; and anti-tick vaccines. Changes in agricultural practices as well as environmental and ecological conditions promoting the abundance of white-tailed deer (WTD) and free-ranging non-native ungulates help sustain CFT populations in south Texas even in the absence of cattle. Evidence based on serologic and molecular findings revealed the presence of B. bovis-like organisms in WTD. These events represent serious complicating factors for eradication efforts. A critical assessment of traditional approaches is required to enable strategies for sustainable CFT eradication. For example, extensive surveillance on WTD and non-native ungulates throughout the year would enhance our understanding of CFT epidemiology along the U.S. – Mexico border. Similarly, partnerships with wildlife experts will facilitate the development of management practices to mitigate the risk for eradication failure associated with WTD as hosts for CFT. Current research efforts are expected to deliver the tools veterinary regulatory agencies need to ensure continued success with the mission to keep the U.S. free of CFT. Research supported in part by USDA-AFRI grant no. 10400992.