Overall prognosis in patients with carcinoma of the esophagus and Gastroesophageal junction remains poor mainly because of the late presentation and advanced stage of the disease at the time of diagnosis. Over the last decades, clinical staging has improved, especially since the introduction of CT scan and echo-endoscopy; however, the clinical definition of potential curative tumors still remains unsatisfactory. More recently, the introduction of PET scanning seems to offer better perspective for more precise staging and evaluation of response. In centers with large experience, cure rates today are exceeding 30% after primary surgery. To improve the cure rate, much attention is paid to neoadjuvant multimodality regimens. In resectable tumors, induction therapy offers little or no benefit. In locally advanced tumors especially, the combination of induction chemoradiotherapy results in a complete response in a substantial number of patients. This subset of patients seems to benefit in terms of survival and cure, whereas the others do not. Future research, therefore, needs to focus on early identification of responders (e.g., through molecular biology) and new chemotherapeutic drugs with higher impact on tumor response and fewer side effects.