Progress has been made in the treatment of locally advanced esophageal cancer. Preoperative and postoperative chemotherapy also appears to improve survival in gastroesophageal junction adenocarcinoma compared to surgery alone. Adding radiotherapy to preoperative chemotherapy enhances rates of curative resection, achieves measurable rates of pathologic complete response, and recent trials indicate a survival benefit for preoperative chemoradiotherapy compared to surgery alone in esophageal cancer. Given the achievement of pathologic complete responses with combined chemoradiotherapy in esophageal cancer, recent trials have evaluated the contribution of surgery after chemoradiotherapy. With currently available systemic therapy for squamous cancers of the esophagus that respond to combined chemoradiotherapy, there is no clear survival benefit for the addition of surgery after chemoradiotherapy despite improvements in local tumor control with the addition of surgery. Surgery may salvage nonresponding patients with biopsy-positive residual disease. For adenocarcinoma of the esophagus, a histology with consistently lower rates of pathologic complete response than squamous cell cancer, surgery appears to play a greater role. Trials are now evaluating the use of newer chemotherapy agents combined with radiotherapy, including taxanes, irinotecan, and oxaliplatin. Response on postiron emission tomography early on during induction chemotherapy may be a strong prognostic measure of outcome. Targeted agents, including monoclonal antibodies that target the epidermal and vascular endothelial growth factor receptors, are in active development in phase II and III trials.