In the United States and other Western countries, there has been a remarkable change in the epidemiology of esophageal cancer over the past 50 years. Adenocarcinoma of the esophagus and gastroesophageal junction has replaced squamous cell as the most common type of esophageal cancer in the United States, and the incidence of esophageal adenocarcinoma is increasing faster than that of any other malignancy. Risk factors include gastroesophageal reflux disease and obesity. The increasing incidence of esophageal adenocarcinoma and a greater understanding of its underlying biology provide opportunities to devise treatment strategies that maximize survival and minimize morbidity. However, rational use of available endoscopic procedures, esophagectomy, and chemotherapy and radiotherapy requires a comprehensive understanding of the disease.