Patients with head and neck cancer (HNC) receiving radiation therapy (RT) alone or with concurrent chemotherapy (CRT) often develop mucositis that may lead to unplanned treatment interruptions and/or chemotherapy dose reductions. Some RT schedules have included planned treatment breaks to allow normal tissues to recover from these toxicities. These decreases in treatment intensity, however, may reduce rates of locoregional tumor control and survival. Any treatment gaps allow for tumor repopulation, which may also promote regrowth of chemotherapy-resistant populations. Therefore, any potential benefits of high-intensity therapy may be lost due to interruptions in RT or reduced chemotherapy dose intensity, unless the treatment intensity is sufficient to offset interval tumor repopulation. Most patients undergoing RT alone and virtually all undergoing CRT--particularly those with HNC--will develop mucositis, which doubles the risk of reduction in treatment intensity and can increase the rate of hospitalization and the use of feeding tubes or total parenteral nutrition. Many of these patients with severe mucositis will require a break in treatment or change in administration schedule to alleviate symptoms. Effective prophylaxis or treatment could reduce the probability of treatment breaks and dose reductions and thus improve outcomes.