Despite the indisputable and well-known advantages of general anesthesia in thoracic surgery, this can trigger some adverse effects including an increased risk of pneumonia, impaired cardiac performance, neuromuscular problems, mechanical ventilation-induced injuries, which include barotrauma, volotrauma, atelectrauma, and biotrauma. In order to reduce the adverse effects of general anesthesia, thoracic epidural anesthesia has been recently employed to perform awake thoracic surgery procedures including coronary artery bypass, management of pneumothorax, resection of pulmonary nodules and solitary metastases, lung volume reduction surgery, and even transsternal thymectomy. The results achieved in this early series have been encouraging, although indications and many pathophysiologic aspects remain to be elucidated. In this review we have tried to provide a first-step analysis of the anecdotal reports available in the literature on this topic. We also desired to provide insights into the main physiologic effects of awake thoracic surgery with epidural anesthesia, with particular attention to the several issues raised by its application in patients with chronic obstructive pulmonary disease, which can represent one of the most stimulating challenges in this setting.