Multiple trials of traditional cancer therapies for malignant pleural mesothelioma (including surgery, radiation therapy, and chemotherapy) have not convincingly demonstrated that any one treatment is superior to supportive care alone. Although there have been reports of long-term survivors who were treated with aggressive surgery combined with radiation and aggressive multi-agent chemotherapeutic regimens, these patient populations are highly selected and results cannot be generalized to a larger population. Despite attempts to use aggressive multimodality therapies, disease recurs in most patients. Local failure in particular is a large part of the natural history of mesothelioma, especially after surgery alone. Therefore, one of the major considerations in the development of new treatments is the inclusion of aggressive local therapies. Photodynamic therapy (PDT), a local treatment modality, is being evaluated as an adjuvant therapy to surgical resection. Clinical use of PDT requires the use of a photosensitizing agent and light of a wavelength specific to the absorption characteristics of the sensitizer in the presence of oxygen. The treatment effect of PDT is superficial, mostly because of the limited depth of light absorption in tissues. Therefore, it is theoretically an ideal treatment for tissue surfaces and body cavities after surgical debulking procedures. One theoretical advantage of PDT is that it can be used to treat the lung surface after a pleurectomy; therefore, patients may be treated with a pleurectomy rather than with an extrapleural pneumonectomy. Several studies have evaluated the efficacy of PDT in the treatment of mesothelioma. Clinical studies have not proven convincingly that the use of PDT is superior to the use of other adjuvant therapies or to surgery alone. The advent of newer photosensitizers and improved laser technology has led to a renewed interest in evaluating PDT. Additional studies are necessary to determine the role of PDT in the treatment of mesothelioma.