Surgery is the treatment option most likely to be associated with prolonged remission in patients with malignant pleural mesothelioma. However, it remains investigational and must always be combined with other modalities to treat the microscopic disease that remains after the most aggressive operations. Improvements in quality of life for appropriate patients with this rare yet incurable cancer may be obtained with less drastic lung-sparing surgical procedures along with intraoperative use of photodynamic therapy (PDT). Very encouraging survival results have been obtained with the combination of surgery and PDT, which requires the well-orchestrated collaborative effort of an extensive team of professionals, from thoracic surgeons and radiation oncologists to basic science researchers. Multi-institutional trials are necessary to duplicate these early findings and shed more light on the tumor-directed immune response of this surgically based multimodal treatment.