The normal squamous esophageal epithelium reacts as a chronic inflammation to the severe gastro-esophageal reflux. Esophagitis will progress to Barrett metaplasia in 10% of patients who would be of minor clinical interest if it then did not advance to low, high grade dysplasia and invasive carcinoma. The rise of esophageal adenocarcinoma (EAC) incidence surpasses any other cancer, including melanoma, lymphoma and small cell lung cancer. There is no clear proof that medical therapy could prevent the neoplastic progression. It seems that this population has a variable answer to proton pump inhibitors therapy. A multimodal approach of Barrett's esophagus with high grade dysplasia is required, including endoscopic mucosal resection, photodynamic therapy and thermal ablation. Photodynamic therapy could be used for the management of patients with high grade dysplasia, early EAC, local recurrence post radical therapy, microscopic involvement of tumor borders post radical resection, patient unfit / unwilling to undergo surgery. The palliation of non-resectable EAC by stenting represents the first choice. The correction of the malignant esophageal obstruction improves the symptomatology and life quality, but not survival. Because of the dismal prognosis and the frequent treatment failure of conventional treatment strategies, it seems reasonable to look for new palliative strategies.