The modern era of cardiac surgery is largely considered to have begun in the animal research laboratories. Today, animal models provide the ultimate preclinical assessment for the study of cardiovascular disease, pharmaceuticals, mechanical devices, and therapeutic procedures. This chapter was designed to provide readers and potential investigators crucial insights into the process of matching an experimental hypothesis to an animal species that will serve as the most appropriate model for specific cardiovascular diseases or for testing a given medical device. A review of the current animal models used in cardiac research is provided and arranged by disease state. Critical factors, including cost, reproducibility, and degree of similarity of the model to human disease are discussed; thus, this chapter can be utilized as a guide in planning research protocols.