The Tasmanian devil, Australia’s largest remaining marsupial carnivore, faces extinction in the wild due to the emergence of a new infectious disease. Devil Facial Tumour Disease (DFTD) is a contagious cancer that is spread as an allograft during biting. Devils have low genetic diversity at the Major Histocompatibility Complex (MHC). We originally proposed that devils were essentially immunological clones, and that cancer cells were able to pass between unrelated animals without triggering an immune response due to this lack of MHC diversity. The discovery of MHC-disparate animals in northwestern Tasmania raised hopes that some of these animals may be able to mount an immune response against DFTD. Indeed, the frequency of disease in these populations remains low. However, we have recently shown that the tumour is able to evade the immune response in MHC disparate animals through the down regulation of cell surface MHC. I will discuss how the use of genomics and transcriptomics has helped us to understand the disease, its evolutionary trajectory and played a pivotal role in our quest to save the species from extinction.