The administration of many chemotherapy regimens may be complicated by toxicities that limit clinicians' abilities to deliver the most effective doses of active agents. Oral mucositis remains the dose-limiting toxicity of a variety of chemotherapeutic regimens and may result in significant morbidity, impaired nutrition, treatment delays, and dose reductions. In this report, the mechanisms of both direct and indirect stomatotoxicity are reviewed and efforts are made to help identify patient-related and treatment-related factors that predispose patients to oral mucositis. Last, various approaches to prevent and treat chemotherapy-induced mucositis are reviewed.