Photodynamic therapy (PDT) is a treatment modality that utilizes a photosensitizing drug activated by laser-generated light and is proving effective for oncologic and nononcologic applications in the gastrointestinal tract. This article provides an overview of the most frequently used photosensitizers and clinical PDT studies in the upper gastrointestinal tract. In the future, the best indications for PDT in the esophagus will not comprise the palliative treatment of obstructing tumors but precancerous lesions such as Barrett's esophagus with or without dysplasia and early cancer. PDT might establish itself as a minimally invasive treatment alternative compared with surgery for high-grade dysplasia or early mucosal cancer of the esophagus.