Artificial ventilation using intermittent positive airway pressure is the mainstay support of patients in respiratory failure. By maintaining alveolar ventilation and alveolar stability, positive airway pressure can sustain respiratory gas exchange between the lungs and circulation, thereby supporting pulmonary homeostasis in patients who would otherwise be unable to maintain oxygen transfer and CO2 elimination. However, positive-pressure ventilation (PPV) also results in complex cardiovascular interactions. More often than not, these interactions impede blood flow through ventilated lungs and reduce global cardiac output. Although arterial oxygen content is adequately sustained because oxygen delivery is equal to the product of arterial oxygen content and cardiac output, global oxygen delivery may be reduced by PPV because of a decrease in cardiac output. Because a primary function of the cardiovascular-respiratory system is to deliver sufficient amounts of oxygen to meet systemic metabolic demands, measurement of arterial blood gases alone in monitoring ventilatory support is inadequate in assessing the cardiopulmonary effects of PPV. Clear understanding of cardiopulmonary interactions associated with mechanical ventilation is required in the rational management of critically ill ventilator-dependent patients. The hemodynamic effects of mechanical ventilation are complex and cannot be explained in terms of the interactions of single hemodynamic processes and cardiac function. However, when considered in this manner, such interactions can be understood more easily. In most patients it is usually clear which process is dominant, permitting adjustments in overall therapy in order to optimize care. This review identifies these interactions and demonstrates which are dominant in specific clinical scenarios.