Although cancer rarely acts as an infectious disease, a recently emerged transmissible cancer threatens the persistence of Tasmanian devils (Sarcophilus harrisii). Devil facial tumor disease (DFTD) has swept across nearly the entire species range, causing a population decline of 80 percent in just 20 years. Using high-throughput genomic sequencing approaches, we have detected evidence for rapid evolution in response to DFTD as well as a genetic basis for variation in disease-related traits. First, we applied a genome scan approach in three populations for which we have devil samples from both before and after DFTD outbreak, and we identified two genomic regions showing strong signatures of rapid parallel response to selection. Both regions contain candidate genes with immune and cancer-related functions. We have expanded this list of candidate loci under selection by targeting regions of the genome across several more independent populations. Further, we have conducted genome-wide association mapping of disease- related phenotypic traits across several populations. Key traits, including time of survival with disease and tumor growth rate, show a significant genetic basis and association with a relatively small number of major-effect loci. Our results suggest the presence of standing genetic variation that could facilitate the evolution of resistance and/or tolerance to DFTD in devil populations, providing hope for the persistence of devil populations in the face of this devastating disease.