Video-assisted thoracoscopic major lung resection for early stage non-small-cell lung carcinoma has been associated with less postoperative pain, better preserved pulmonary function, shorter hospital stay, and enhanced tolerance of adjuvant chemotherapy compared to thoracotomy. Initial concerns regarding safety, oncological clearance, and cost effectiveness were unfounded. Several recent trials have reported improved long-term survival in patients with early stage non-small-cell lung carcinoma undergoing video-assisted thoracoscopic major lung resection, compared to the open technique, although there are inconsistencies. Interestingly, the immune status and autologous tumor killing ability of lung cancer patients have previously been associated with long-term survival. Video-assisted thoracoscopic lung resection results in an attenuated postoperative inflammatory response, but more importantly, it better preserves postoperative immune function. Circulating natural killer and T-cell numbers, T-cell oxidative activity, and levels of immunochemokines such as insulin growth factor binding protein-3 are higher after video-assisted thoracoscopic surgery than after thoracotomy. Recently, interest has developed in the role of the angiogenesis factor, vascular endothelial growth factor, after cancer surgery. Whether differences in immunological and biochemical mediators contribute towards improved long-term survival following video-assisted thoracoscopic major lung resection for cancer remains to be confirmed.