It is generally accepted that thoracic surgery for lung cancer produces some of the most intense and difficult perioperative and chronic pain challenges. In the acute period of recovery, practitioners must optimize patient comfort and pulmonary function. This can be achieved through a combination of systemic treatment and regional analgesic options. Thoracic surgery also causes relatively high levels of persistent postsurgical pain. Many of the cases of persistent pain have a clear neuropathic pain mechanism, but a significant number of cases do not. While persistent pain correlates directly with the extent of operative trauma, even video-assisted thoracoscopic surgery approaches can cause chronic pain. Persistent pain is treated with medical and interventional therapies customized to an individual patient’s complaints and medication tolerance.