AbstractSince the publication of the last edition of the Handbook of Physiology, lung transplantation has become widely available, via specialized centers, for a variety of end‐stage lung diseases. Lung volume reduction surgery, a procedure for emphysema first conceptualized in the 1950s, electrified the pulmonary medicine community when it was rediscovered in the 1990s. In parallel with their technical and clinical refinement, extensive investigation has explored the unique physiology of these procedures. In the case of lung transplantation, relevant issues include the discrepant mechanical function of the donor lungs and recipient thorax, the effects of surgical denervation, acute and chronic rejection, respiratory, chest wall, and limb muscle function, and response to exercise. For lung volume reduction surgery, there have been new insights into the counterintuitive observation that lung function in severe emphysema can be improved by resecting the most diseased portions of the lungs. For both procedures, insights from physiology have fed back to clinicians to refine patient selection and to scientists to design clinical trials. This section will first provide an overview of the clinical aspects of these procedures, including patient selection, surgical techniques, complications, and outcomes. It then reviews the extensive data on lung and muscle function following transplantation and its complications. Finally, it reviews the insights from the last 15 years on the mechanisms whereby removal of lung from an emphysema patient can improve the function of the lung left behind. © 2011 American Physiological Society. Compr Physiol 1:1383‐1412, 2011.