This article gives a brief discussion of "state-of-the-art" therapeutic strategies for esophageal and gastroesophageal junction tumors, with an emphasis on combined-modality therapy. In addition, we review the results of a multimodality trial conducted using a new agent against esophageal cancer, oxaliplatin. In this trial, the emphasis was on the efficacy and toxicity of oxaliplatin in combination with protracted infusion 5-fluorouracil and radiation. A secondary endpoint of the study was the relationship between efficacy and toxicity to specific intratumoral gene expressions within the primary esophageal tumor.