Clinicians caring for patients with cardio-pulmonary disease invariably must manage the respiratory system. Doing so requires a basic understanding of physiology and the interaction of the heart and lung. The present chapter begins with rudimentary concepts of respiratory physiology, focusing on, gas exchange, pulmonary mechanics, and cardio-pulmonary interactions. These are used to develop an approach to mechanical ventilation and routine perioperative respiratory care of the patient having undergone a cardio-pulmonary procedure. The final section of this chapter addresses specific respiratory challenges encountered in caring for the critically ill cardiothoracic patient in addition to contemporary management strategies.