In veterinary medicine, irreversible electroporation (IRE) applications have been evaluated in several early phase clinical trials evaluating the safety and feasibility of treatment of solid tumors located within different organ systems. These clinical trials support the use of IRE as a safe and effective alternative treatment option for tumors that are otherwise not amenable to current standard of care therapy. The recent development of high-frequency irreversible electroporation (H-FIRE) has made treatment delivery even more feasible for veterinary clinical patients. Here, we provide an overview of treatment planning and techniques while acknowledging current limitations associated with treatment delivery, followed by a review of IRE applications in veterinary clinical trials of spontaneous cancers. Lastly, we review the application of IRE in preclinical normal animal models or experimentally induced tumors as results of these studies may help facilitate translation of IRE into standard clinical practice.