Specific indications for a second or remediastinoscopy include an inadequate first procedure, metachronous second primary or recurrent lung cancer, lung cancer after unrelated disease, and restaging after induction therapy. Nowadays, restaging is the most frequent indication for remediastinoscopy. Only patients with proven mediastinal downstaging will benefit from a subsequent surgical resection. In contrast to imaging or functional studies, remediastinoscopy provides pathological evidence of response after induction therapy. Although technically more challenging than a first procedure, remediastinoscopy can select patients for subsequent thoracotomy and provides prognostic information. Technically, mediastinal dissection is usually started at the left paratracheal side to avoid the innominate artery. Under the aortic arch, dissection proceeds in the pretracheal plane until the subcarinal nodes are reached. Sensitivity of a second mediastinoscopy is lower than a first procedure but in the most recent series it is higher than 70% with an accuracy around 85%. Survival also depends on the findings of remediastinoscopy, patients with persisting mediastinal involvement having a poor prognosis. An alternative approach consists of the use of minimally invasive staging procedures as endobronchial or endoscopic esophageal ultrasound to obtain an initial proof of mediastinal nodal involvement. Mediastinoscopy is subsequently performed after induction therapy to evaluate response. In this way, a technically more difficult remediastinoscopy can be avoided.