At present, approximately one in two households owns a pet with about quarter of these pets being dogs or cats. Due to the high degree of inbreeding in domestic dogs and cats, over 350 of the diseases in pets also occur in human patients. Unlike transgenic mice where specific genes are knocked in or knocked out to cause disease, the genetic mutations in dogs and cats that leads to naturally occurring diseases may not be elucidated. However, naturally occurring diseases in pets offers several advantages over purpose bred animals for probing physiology. In particular, pets with naturally occurring diseases often have many of the underlying co-morbidities seen in human patients, are treated with a variety of medications, and experience varying environments that in turn alter genetic expression of disease. For imaging applications, dogs and cats are sufficiently large enough to use clinical imaging equipment and pediatric or adult devices with little to no modifications. In particular, more than 50% of dogs >10 years of age will develop malignancies. For example, osteosarcoma (OSA) is the most common bone tumor in dogs and has many similarities to human OSA.(1) An example of MRI-guided cryotherapy of a bone tumor is show in Fig 1. While ischemic heart disease and thromboembolic disease are relatively rare in pets without underlying renal disease and neoplasia, many other forms and risk factors of cardiovascular disease, such as diabetes mellitus (2), mitral valve disease (3), and dilated cardiomyopathy (4), are prevalent in pets. Diseases showing similarities to neurological diseases in man, such as multiple sclerosis, Alzheimer’s (5), and spinal cord injury, are also prevalent in pets. Examples of potential stem cell and drug therapy targets and monitoring with imaging will be presented. Clinical trials in pets must often undergo similar regulatory processes for device and drug approval and ethical review, which may vary by local regulatory bodies. In some cases, preclinical data in research animals may be neccessary to perform clinical trials in pets, which is similar to tradition drug and device development for translation to human studies. However, the use of spontaneous disease in pets may be not only informative for human clinical trials but also provide new therapies for treatment of diseases in domestic animals.