Radiation therapy remains the primary method of treatment for patients with head and neck cancer. The tissue destruction and functional alterations in the oral cavity lead to the development of oral mucositis. The purpose of this review is to describe the mechanisms, risk factors, prevalence, and magnitude of radiation therapy-related oral mucositis and its morbidities in patients with head and neck cancer. The review concludes with a discussion of the implications for clinical practice. This review provides cancer nurses with the information necessary to identify patients with head and neck cancer who are at high risk for oral mucositis and the significant comorbidities associated with this complication of radiation therapy.