The chestnut blight’s devastating effect on the American chestnut is a classic example how an invasive pathogen can alter forest ecosystems and disrupt people’s livelihoods. Because of the American chestnut tree’s environmental, economic, and social importance, many tools have been brought to bear on the chestnut blight problem, but with minimal success. Initiated by members of the public, my colleagues and I focused on enhancing blight tolerance, considered a more evolutionarily sustainable type of defense mechanism. To enhance blight tolerance, a gene encoding an enzyme that counteracts the pathogen’s key virulence factor, oxalate, was added using the tools of genetic engineering. This oxalate oxidase (OxO) gene came from bread wheat (Triticum aestivum) but is also common to many crop and wild plants, fungi, and bacteria. Therefore OxO is not new to our food or the environment. Leaf and small stem assays demonstrate enhanced blight tolerance levels in transgenic American chestnut similar to those found in the blight-resistant Chinese chestnut (C. mollissima). Several environmental impact experiments have been completed demonstrating no significant differences between the transgenic and non-transgenic chestnut. The next step is to have the trees reviewed by up to three federal regulatory agencies, the USDA, EPA, and FDA. Once approved, these blight-tolerant American chestnut trees may be used to help rescue the genetic diversity and local adaptations in the remnant, surviving population of American chestnut and serve as an example to help other threatened tree species.