The induction and maintenance of anesthesia, surgical requirements, and patients’ unique pathophysiology all combine to create a setting in which our accumulated knowledge of respiratory physiology and lung mechanics take on immediate and central importance in patient management. In this review we will take a case-based approach to illustrate how the complex interactions between anesthesia, surgery, and patient disease impact patient care with respect to pulmonary pathophysiology and clinical decision-making. We will examine two disparate scenarios: a patient with chronic obstructive pulmonary disease undergoing a lung resection, and a patient with coronary artery disease undergoing cardiopulmonary bypass. In each example we will illustrate how important concepts in pulmonary physiology and respiratory mechanics impact clinical management decisions.