For many years, scientists have been investigating use of drugs to protect normal tissue from injury during radiation therapy, thereby increasing the amount of radiation that can be safely administered to patients. Despite the introduction of modern shielding techniques, dose modulation, and tissue-volume mapping, a small amount of normal tissue surrounding the target volume is inevitably irradiated during treatment, which can lead to severe side-effects. The most recent chemical radioprotector to become available clinically is amifostine. On the basis of efficacy data from a phase III randomised trial in patients with head and neck cancer, which showed reduced acute and chronic xerostomia with preserved antitumour response, some institutions are now adding amifostine to their chemoradiation regimens. However, much controversy surrounds the use of this drug. Some investigators are worried that radioprotectors may stop tumour tissue responding to radiation and therefore reduce treatment effectiveness. Moreover, amifostine opponents argue that the evidence is insufficient to justify routine use of this drug. In this Debate, David Brizel, who worked on the phase III amifostine efficacy study, and Jens Overgaard, a vehement opponent of amifostine therapy, provide thought-provoking arguments for two opposing perspectives on this contentious issue.