Spontaneously occurring cancers in animals provide a unique set of opportunities for insights into basic biology, pathogenesis and for development of effective therapies. An ever-growing number of companion animals present with a wide range of cancers to veterinary clinics, needing expert care and treatment. These spontaneous cancers represent parallel diseases to human diseases, and have several key advantages, including a full immune system, which is being more and more recognized as a major advantage over mouse model systems given the developments in recent immunotherapeutic approaches. In addition, the veterinary oncology patients present with the total complexity of cancer, including tumor heterogeneity as well as constitutive heterogeneity among individuals. Furthermore, dogs and cats develop cancer in the context of a shared environment with humans. Some dog breeds have a greater incidence of certain cancers and may lead us to dissect genetic determinants of predisposition to cancer. In the context of drug discovery, companion animals allow for novel therapeutic approaches to be tested in the naïve patient as well as those relapsing or not responding to conventional treatments. Furthermore, some rare cancers are more abundant in the canine population, allowing for clinical trials to be launched more effectively. In his presentation, I will share some of our studies focusing on drug discovery and repurposing efforts in a number of canine and feline cancers, including osteosarcoma, histiocytic sarcoma and lymphoma in dogs and lymphoma and squamous cell carcinoma in cats with implications for the parallel diseases in humans.