Devil facial tumor disease (DFTD) is a transmissible cancer that threatens the persistence of Tasmanian devils (Sarcophilus harrisii). Using genomic techniques, we have detected evidence for rapid evolution in response to DFTD as well as a genetic basis to isease-related phenotypes. Recently a second independently derived transmissible cancer was discovered in devils, raising the hypothesis that this a recurring selective force. We have found widespread evidence for historic selection in the devil genome, but it is not trongly associated with the genes currently responding to DFTD. These results hold important implications for management of devil populations for the conservation of adaptive potential in the face of transmissible cancer and other threats.