The incidence of esophageal adenocarcinoma is rising in the United States and Western countries. Significant differences exist between esophageal adenocarcinoma and squamous cell carcinoma in the molecular mechanisms responsible for the tumorigenesis process. State-of-the-art techniques such as gene microarrays and proteomics will greatly aid in the development of new therapies targeting specific molecular pathways,ultimately leading to improved survival in patients who have esophageal cancer.