The incidence of esophageal adenocarcinoma (AC) has increased dramatically in the Western world over the past 20 years and the majority of these cancers arise on the background of the preinvasive lesion Barrett's esophagus. The epidemiologic factors that contribute to an individual's susceptibility for Barrett's esophagus and associated cancer are likely to be multifactorial. However, the short time frame over which the incidence of adenocarcinoma has increased, and the increase across populations, provides a strong argument for environmental factors as etiologic agents, perhaps interacting with genetically determined characteristics that define personal susceptibility. In this review we discuss the epidemiologic evidence for the proposed demographic and environmental risk factors for the development of both Barrett's esophagus and AC. The current evidence suggests that significant risk factors include male sex, Caucasian race, and the presence of duodenogastroesophageal reflux disease. The susceptibility for reflux disease may in turn be influenced by factors such as obesity, the use of drugs that lower the lower-esophageal sphincter tone, and a protective effect of Helicobacter pylori colonization. There appears to be a weak association between smoking and AC. The role of dietary factors has not been studied adequately and deserves further attention. An understanding of the factors that predispose to the development and progression of Barrett's esophagus is crucial to the implementation of effective screening and prevention programs.