Esophageal cancer is one of the ten most frequent tumors worldwide. There are two major histologies: squamous cell carcinomas, which appear more frequently in the upper part of the esophagus, and adenocarcinomas, which are predominantly found in the distal part and at the gastroesophageal junction. Most patients suffer from locally advanced tumors, for which the prognosis is still poor with a 5-year survival rate of 15–25%. Treatment is based on histology, tumor stage, location of the tumor, performance status, age, and comorbidities and it consists of surgery, chemotherapy, or radiotherapy or a combination of these. Over the past decades, neoadjuvant radiochemotherapy followed by surgery became standard of care in patients with locally advanced squamous cell carcinomas suitable for surgery. The treatment of locally advanced adenocarcinomas and junctional tumors is still under debate and consists of either perioperative chemotherapy or neoadjuvant chemoradiotherapy followed by surgery. In patients not suitable for surgery, definitive radiochemotherapy is considered the treatment of choice. Modern radiotherapy in esophageal cancer is increasingly conformal and the dose at organs-at-risk could be reduced over the years to lower the rate of treatment-related side effects. Individualization of treatment and new combinations of systemic agents are under investigation to improve treatment outcome.