There is no international consensus on the optimal management of operable esophageal cancer. Surgery alone is associated with a poor prognosis and is only appropriate in patients with very early-stage disease. Data from randomized phase III clinical trials support the use of neoadjuvant chemotherapy, neoadjuvant chemoradiation and perioperative chemotherapy for patients with adenocarcinomas of the esophagus and neoadjuvant chemotherapy, neoadjuvant chemoradiation or definitive chemoradiation for localized squamous cell carcinomas (SCC). Meta-analyses of published clinical trials have not assessed the role of perioperative chemotherapy and definitive chemoradiation, but have demonstrated a comparable survival benefit from neoadjuvant chemotherapy and chemoradiation for operable adenocarcinomas of the esophagus. A greater benefit for neoadjuvant chemoradiation compared with chemotherapy, however, was noted for localized SCC. In this Review, we discuss the data available from clinical trials and meta-analyses and how they inform current clinical practice.