Most patients with locally advanced esophageal cancer die from their disease, despite complete surgical extirpation of tumor or institution of aggressive, multimodality treatment. Nevertheless, a favorable trend emerging in the management of such patients is that "more therapy is better." This review describes several studies indicating that aggressive, combined-modality therapy provides a survival advantage for patients with locally advanced esophageal cancer. An ongoing North Central Cancer Treatment Group trial further capitalizes on the concept of "more is better," and tests subcutaneous amifostine (Ethyol, WR-2721; MedImmune, Inc, Gaithersburg, MD) to balance the need for aggressive therapy with the need to mitigate associated toxicity.