Photodynamic therapy (PDT) is a minimally invasive and promising new modality to combat cancer. Upon illumination and in the presence of oxygen, the tissue-localized nontoxic sensitizer generates cytotoxic reactive oxygen species, and as a result, the selective destruction of a targeted tumor may be achieved. The major advantages of PDT compared to traditional standard of care for cancer treatment are higher selectivity and lower toxicity. The high degree of selectivity offered by this modality has been applied to cancer diagnosis by fluorescence.This article is a review the clinical effectiveness of PDT in the treatment of Barrett's esophagus and the following cancers: esophageal, gastric, biliary tract, pancreatic, and colon. This review highlights the clinical responses to PDT and discusses the possibility of enhancing the efficacy of treatment by combination with targeted therapy.