Established over 117 years ago, the Cattle Fever Tick Eradication Program (CFTEP), originally called the U.S. Tick Eradication Program, was the first parasite eradication program of veterinary importance in the United States and is considered to be one of the greatest disease eradication programs of all time. With initial funding of only $82,500, the program’s utilization of pasture vacation and dipping of cattle in acaricide has been extremely successful for controlling Rhipicephalus (Boophilus) microplus (Canestrini) and R. (B.) annulatus (Say), collectively known as cattle fever ticks, on cattle along the Texas border with Mexico for decades. Recently rising populations of white-tailed deer and other exotic ungulate species in South Texas have compromised the success of the program. An overview of the history of the CFTEP, the continued importance of controlling cattle fever ticks in South Texas, and present challenges to the success of the program will be highlighted.