Barrett's esophagus with high-grade dysplasia is a well-known risk factor for the development of esophageal adenocarcinoma, which has become the predominant form of esophageal cancer in the United States. This review addresses four major fundamental issues that shape our treatment decisions regarding high-grade dysplasia within Barrett's esophagus: (1) the poorly defined natural history of high-grade dysplasia in its progression to adenocarcinoma, (2) the potentially high morbidity and mortality of esophageal resection for high-grade dysplasia, (3) the difficulty in detecting cancer among dysplastic cells during endoscopy, and (4) the controversial role of endoscopic mucosal ablative therapy for high-grade dysplasia. Until there are more accurate surveillance methods, better biochemical or molecular markers in predicting cancerous progression, or more effective minimally invasive methods of treatment, esophagogastrectomy must be considered the standard means of managing patients with Barrett's esophagus and high-grade dysplasia. Regular rigorous systematic surveillance and endoscopic mucosal ablation are alternative treatment options that are available but should be used only under strict conditions. The decision to proceed in a certain direction is quite complex and challenging and ideally requires the feedback of patients who are properly educated about the controversies surrounding this disease.