Oral mucositis refers to erythematous, erosive, and ulcerative lesions of the oral mucosa seen in two patient populations: (1) head and neck cancer patients undergoing radiation therapy to fields involving the oral cavity, and (2) patients receiving high-dose chemotherapy for cancer. Oral mucositis is a significant and dose-limiting toxicity of cancer therapy, with important clinical and economic implications. This article reviews the current knowledge on the pathogenesis, clinical presentation, diagnosis, and management of oral mucositis.