Animal models have significantly advanced our understanding of the mechanisms of atherosclerosis and restenosis formation and the evaluation of therapeutic options. The current focus of research is on preventive strategies against restenosis and includes pharmacologic and biologic interventions directed primarily against smooth muscle cell proliferation, endovascular devices for recanalization and/or drug delivery, and an integrated approach using both devices and pharmacobiologic agents. Devices aimed at the percutaneous endoluminal exclusion of aortic aneurysms have also generated interest recently. The experience over many decades with animal models in vascular research has established that a single, ideal, naturally available model for atherosclerosis, restenosis, or for that matter aneurysm formation, does not exist. Presently, rabbits and pigs are favored for the former two areas of study, and dogs and sheep appear to provide suitable models for testing devices for endoluminal repair of aneurysms. The development of transgenic variants of currently available models may widen our options in the future. Nevertheless, an appreciation of the individual features of natural or stimulated disease in each species is of the utmost importance for the proper design and execution of relevant experiments.