Patients who have a lung cancer in the residual lung after pneumonectomy should not be automatically excluded for surgical consideration. These patients should be carefully staged and evaluated physiologically. The most important initial differentiation is to distinguish a true second primary lung cancer from metastatic recurrent lung cancer. Meticulous staging with chest CT, PET, brain MRI, and mediastinoscopy should be able to successfully exclude metastatic disease, multifocal disease, or locally advanced tumors. Only patients who have stage I disease are candidates for this type of extended resection. Ideally, these patients should have small peripheral tumors that can be encompassed with a low-volume wedge resection. More extended resections, such as segmentectomy or right middle lobectomy, may be considered in some patients but seem to bear a higher operative morbidity and mortality. The need for an upper or lower lobectomy after contralateral pneumonectomy is probably an absolute contraindication to surgical resection. To tolerate pulmonary resection after pneumonectomy, and to obtain the desired survival benefit, patients should have a good to excellent performance status, no serious comorbidities, and a ppoFEV1 greater than 1.0 L/second. In these highly selected patients, pulmonary resection after pneumonectomy can be accomplished with an acceptable operative morbidity and mortality and, in true cases of metachronous second primary lung cancers, may achieve a 5-year survival rate of up to 50%.