Despite advances during the last 2 decades in every aspect of cardiovascular research (interventional cardiology, cardiopulmonary resuscitation, and so forth), Western societies still are plagued by the consequences of cardiovascular disease. Consequently the discovery of new regimens and therapeutic interventions is of utmost importance. Research using human subjects is associated with substantial methodologic and ethical considerations, and the quest for an appropriate animal model for the human cardiovascular system has led to swine. The porcine heart bears a close resemblance to the human heart in terms of its coronary circulation and hemodynamic similarities and offers ease of implementation of methods and devices from human healthcare facilities. A thorough comprehension of the anatomy and physiology of the porcine cardiovascular system should focus on differences between swine and humans as well as similarities. Understanding these differences and similarities is essential to extrapolating data appropriately and to addressing the social demand for the ethical use of animals in biomedical research.