The incidence of esophageal adenocarcinoma (EAC) has increased in many Western countries and is higher in men than women. Some risk factors for EAC have been identified—mainly gastroesophageal reflux disease, Barrett’s esophagus, obesity, and tobacco smoking. It is not clear whether interventions to address these factors can reduce risk of EAC, although some evidence exists for smoking cessation. Although consumption of alcohol is not associated with EAC risk, other exposures, such as physical activity, nutrition, and medication use, require further study. Genetic variants have been associated with risk for EAC, but their overall contribution is low. Studies are needed to investigate associations between risk factors and the molecular subtypes of EAC. The prognosis for patients with EAC has slightly improved, but remains poor—screening and surveillance trials of high-risk individuals are needed.