Photodynamic therapy (PDT) is a photochemical process that uses a photosensitizer drug activated by laser light to produce mucosal ablation. Porfimer sodium PDT has proved long-term efficacy and durability in the treatment of Barrett’s esophagus and high-grade dysplasia and early esophageal adenocarcinoma. Its use has been limited by serious side effects including prolonged cutaneous photosensitivity and stricture formation. Other photosensitizers with a better safety profile have been used mostly in Europe with limited experience. The future of PDT lies on a better understanding of dosimetry, tissue properties, and host genetic factors.