Modern drug development is plagued by extremely high attrition rates when entering clinical trials. As many as 95% of drugs entering clinical trials fail, including almost 50% of those in phase III. Companion animals with spontaneous diseases analogous to humans offer several advantages when compared to traditional preclinical animal models in proceeding with successful preclinical IND packages. The development of novel innovative therapeutics, such as gene therapies, are not always predictive. Companion animals offer the potential to increase drug efficacy while reducing potential toxicities because they express genetic diversity and share environmental factors with humans. These attributes support the refinement and reduction of induced preclinical animal models. During this presentation, we will discuss some relevant spontaneous companion animal diseases with shared human pathology that could serve as preclinical animal models for human drug development.