This literature review presents an historical perspective and basic principles of the isolated-perfused heart and gives examples of its current usage together with some personal research data. Heart function, both under conditions of health and disease, is regulated at the molecular, cellular, organ and whole organism level. To address regulation of the heart at various levels, a vast variety of experimental models ranging from man to a single molecule are needed. The isolated mammalian heart preparation, perfused with a blood-free medium, whole blood, or blood components according to Langendorff, has provided reliable information on the condition of the working musculature, the conduction system and the coronary vessels in various conditions. Due to the technical ease by which these functions of the heart can be analyzed, the preparation has been frequently used as a research tool. The molecularly based understanding of the heart will hopefully be a source for new treatments of common cardiac conditions, such as heart failure, cardiomyopathy and dysrhythmias. Thus, the isolated-perfused heart will be further used to test the hearts function under various circumstances. Advances in the conditions that increase stability and extend the life of this preparation could also contribute to its prolonged and expandable usage.