The incidence of adenocarcinoma of the esophagus is rapidly increasing in the Western world. In North America and western Europe, a marked shift in the epidemiologic profile of this disease has occurred. In the past, most patients with esophageal cancer were found to have epidermoid carcinoma. These patients frequently abused tobacco or alcohol, had multiple comorbid medical conditions, and were elderly. Over the last 10 to 15 years, a rapid increase in the number of patients having adenocarcinoma of the esophagus has been noted. In contrast, these patients are predominantly young white men from 35 to 55 years old who much less frequently smoke or drink, and many have few or no comorbid medical conditions, are fit, and are able to tolerate aggressive combined therapy. This article focuses on the adenocarcinoma subgroup of patients, although identical therapeutic approaches are being studied in appropriate patients with epidermoid carcinomas.