Esophageal carcinoma is a lethal disease, causing more than 400,000 deaths annualy worldwide. Primary surgery results in microscopically positive resection margins (R1) in 25% patients, and the 5-year OS for such patients rarely exceeds 40%. Definitive or preoperative concurrent chemoradiation followed by surgery results in better survival than single-modality treatments, and thus NCCN recommends concurrent chemoradiation as preoperative or definitive treatment for patients with stage II or III esophageal cancer. However, preoperative concurrent chemoradiation may not be effective in some subgroup of these patients, and its toxicity can increase perioperative mortality and delay or preclude surgery. The ability to distinguish tumors that will respond or not respond to such therapy remains an urgent priority.