Oral mucositis is a common toxicity of high-dose chemotherapy and upper mantle head and neck radiation. Published evidence from the past 14 months provides insight into the multiple possible mechanisms. In addition, the data highlight the clinical importance that this lesion exerts relative to infection risk, quality of life, and cost of care. Oral mucositis has emerged as a dose-limiting toxicity in selected cancer therapy models. Thus, it has direct impact on duration of disease remission, cure rates, and long-term survival. Because of its importance in the clinical setting, oral mucositis remains under extensive laboratory and clinical investigation. Advances in the 1980s relative to infection prevention and reduced duration of profound neutropenia via growth factors have elevated oral mucositis to a prominent toxicity of cancer therapy. A contemporary model for mucositis involving four principal phases was published in 1998. Future research will likely add further insight into this model relative to the roles of mucosal immune dysregulation, colonizing microflora, and wound-healing mechanisms. Basic and clinical studies directed to these several components may well lead to effective preventive strategies in the future, with positive impact on quality of life and survival of cancer patients.