The incidence and mortality related to esophageal adenocarcinoma (EAC) have been increasing in the United States, several European countries, and Oceania for the past 2 to 3 decades. Survival remains dismal, with little improvement during the same time period. Variations in the coding, classification, and detection of gastroesophageal malignancy may have contributed partially to the observed trends. Remarkable differences related to gender, ethnicity, and geography characterize the epidemiology of EAC. Gastroesophageal reflux disease (GERD) is the main risk factor for Barrett's esophagus, which is the only known precursor lesion for EAC. Several risk factors that promote the development of GERD and/or Barrett's esophagus have been proposed to explain these rising trends; these factors include the declining rates of Helicobacter pylori infection, obesity, dietary factors, and certain drugs.