Animal studies suggest that there are two mechanisms for blood flow during CPR: manipulation of intrathoracic pressure and/or direct cardiac-vascular compression. These mechanisms are not necessarily mutually exclusive and may coexist during different phases of prolonged resuscitation. Data in man, however, are inconclusive. Several studies suggest that intrathoracic pressure manipulation is a potent mechanism for blood flow during CPR in man. Other observations support the likelihood of cardiac-vascular compression. In addition, there is a lack of consensus on the best parameter(s) to use in studying the mechanism of flow. Despite these limitations, the better understanding of the physiology of CPR has led, in turn, to the development of more focused mechanical and pharmacological strategies to improve vital organ perfusion during resuscitation.