Amidst increased tensions over the US–Mexico border, a multinational group of over 2500 scientists have endorsed an article cautioning that a hardened barrier may produce devastating ecological effects while hampering binational conservation. In the BioScience Viewpoint, a group organized by Defenders of Wildlife and others called attention to ecological disturbances that could affect hundreds of terrestrial and aquatic species, notably including the Mexican gray wolf and Sonoran pronghorn. For this episode of BioScience Talks, we were joined by Rob Peters, Senior Representative with the Southwest Regional Office of Defenders of Wildlife; Rurik List, Head of the Laboratory of Conservation Biology at the Universidad Autónoma Metropolitana, Lerma Campus; and Sergio Avila, Wildlife Biologist and a Program Manager with Sierra Club, based in Tucson, Arizona. They discussed the article, the potential effects of a border wall, and some of the other challenges of conducting science in the borderlands.