Summary Esophageal adenocarcinoma (EAC) has had the fastest increasing incidence of any solid tumor in the United States in the last 30 years. Long standing gastroesophageal reflux disease is a well-established risk factor with strong associations with obesity, alcohol and tobacco. However, there are likely additional contributing factors. Viruses such as human papillomavirus, ebstein-barr virus and herpes simplex virus have been implicated in the pathogenesis of esophageal cancer. This review will discuss the known literature linking viruses to esophageal adenocarcinoma and consider future relationships such as identifying prognostic and predictive molecular biomarkers to guide therapies.