Human tissues usually represent end-stage disease, therefore, animal models are critical to understanding the disease, and validating interventions. This chapter provides a practical overview of the osteoarthritis models and their advantages and disadvantages. Mechanical models were developed to provide an accelerated, but controlled model of osteoarthritis or, in some cases, to demonstrate the contribution of particular mechanical components or structural elements to the development of osteoarthritis. Surgical models of mechanical instability which are mimics of chronic traumatic osteoarthritis are the most commonly utilized models. Magnetic resonance imaging has been used to describe the progression of osteoarthritis in mice, rat, guinea pigs, rabbits, and dogs. The frequency of osteoarthritis models used in interventions appears to be strongly driven by cost, ease of animal handling, especially of intra-articular injections, rapidity of disease development, and to a lesser extent, availability of the appropriate reagent.