Current therapeutic approaches for lung cancer favor treatment intensification, with the presumption that dose-intense chemotherapy regimens and/or higher radiation therapy (RT) doses or novel fractionation schemes will result in increased patient survival. Also, the trend for non-operative therapy has favored concurrent over sequential regimens. The incidence of severe acute esophagitis in patients treated for lung cancer with standard (once daily) RT alone is 1.3%, and induction chemotherapy increases the risk of severe acute esophagitis slightly over that of standard RT alone. In contrast, a strong radiosensitizing effect of chemotherapy given concurrently with standard thoracic RT (chemoRT) is associated with an incidence of severe esophagitis of 14% to 49%. Acute esophagitis may be severe and disabling, and result in hospitalization, placement of a feeding tube in the stomach or intravenous feedings, and steady supportive care. Also, RT may need to be halted temporarily to allow for healing of the esophageal lining; treatment breaks in turn decrease survival of patients with unresectable lung cancer. Therefore, esophagitis as a dose-limiting toxicity of chemoRT may have a direct impact on tumor control and survival. Aggressive types of RT fractionation have also been associated with worsening esophagitis grades and duration. Moreover, it is commonly assumed in the radiation oncology clinic that the longer the length of the esophagus segment included in the RT field the higher the probability of esophageal toxicity, although differing opinions are commonly expressed. Recent advances in 3-dimensional conformal RT allow a unique chance to gain volumetric data pertaining to organ damage rather than rely on older estimates based on organ length (eg, esophagus) or portion (ie, lung, spinal cord). The Radiation Therapy Oncology Group (RTOG) conducted a large phase III, randomized study RTOG 98-01 examining chemoRT with or without the amifostine (Ethyol; MedImmune, Inc, Gaithersburg, MD), a cyto- and radioprotectant in locally advanced non-small cell lung cancer (n = 243). While amifostine did not significantly reduce severe esophagitis based on National Cancer Institute Common Toxicity Criteria and weekly physician dysphagia logs, swallowing dysfunction over time (based on patient diaries, the equivalent of Esophagitis Index) was significantly lower in the amifostine arm ( P = .03). Therefore, significant progress has been accomplished in our understanding of the basis of esophageal injury resulting from thoracic RT, and future effort may find other effective strategies to either minimize or eliminate esophagitis.