Clinical photodynamic therapy was introduced in the 1970s and has been shown to be an effective treatment modality in a variety of fields in oncology. Photodynamic therapy (PDT) is a local therapy such as radiation and surgery, which involves the photosensitization of neoplastic cells and tissues with porphyrins or related structures that catalyze, upon irradiation by laser, formation of reactive oxygen species. A photosensitizing agent is administered to the patient and after a period of 24-72 h when the concentration of the photosensitizer is maximized in tumor tissue compared with normal tissue, and then the neoplastic mass is exposed to the laser light, which initiates the necrotic process. Despite the ability of PDT to destroy the tumor selectively, it has not been applied widely due to the lack of understanding of its therapeutic mechanism and clinical experiences as well as some limitations of currently available photosensitizers. Nowadays, the number of scientific articles on PDT, regarding clinical applications as well as basic science, made its application increasing. In one of the most suitable indications, lung cancer, PDT is a minimally invasive therapeutic option for the treatment of early cancer in airway and palliation for the endobronchial obstruction from central lung cancer. In esophageal cancer, PDT can also be applied to treat in early stage without muscle invasion or remnant cancer after endoscopic mucosal resection. Besides, PDT can be applied as a part of combined modality such as a neoadjuvant or adjuvant PDT. With the advances of new sensitizers and energy delivery system, clinical application of PDT will expand in near future. This review article will focus on the basic mechanism and the clinical investigations of PDT for the clinicians.