Esophagectomy is a major surgical procedure. Due to the related morbidity and mortality, this operation should be carried out in high-volume referral centers by expert surgeons. Only patients in whom a complete resection is predictable at preoperative staging can consistently benefit from the operation. Chemoradiation therapy should be the first-line approach in patients with locally advanced tumors. A pathological complete response to neoadjuvant therapy is associated with a significantly improved long-term survival.