Newer treatments for head and neck cancers, including altered fractionation and the use of concomitant radiotherapy and chemotherapy, may provide better local–regional tumor control rates; however, patients may experience more frequent and more severe acute toxicities that result in considerable suffering. Through this study, we sought a better understanding of patients’ experiences when undergoing radiotherapy. Personal interviews were conducted with 33 individuals who had received radiotherapy for head and neck cancers. These individuals described their treatment experiences and identified the most troublesome and debilitating side effects of radiotherapy. Overall, lethargy and weakness, dry mouth, mouth sores and pain, taste changes, and sore throat were the most frequently reported troublesome or debilitating side effects. The single most debilitating side effect was oropharyngeal mucositis that was characterized by patients as sore throat, and mouth sores and pain; both negatively affected the patient’s ability to eat and drink, causing many patients to experience significant weight loss. Trends toward more aggressive management of head and neck cancers underscore the need for new and effective therapies for oropharyngeal mucositis occurring in patients receiving radiotherapy.