Oral mucositis (OM) has emerged as a common cause of dose delays and interruptions of cancer therapies such as multicycle chemotherapy, myeloablative chemotherapy, and radiotherapy with or without concurrent chemotherapy of head and neck cancer. Research into both preventive and management strategies has lagged behind research into the common cancer treatment-related morbidities of nausea, vomiting, and cytopenias. This disparity is related to the complex risk assessment of multifactorial patient and treatment factors and different techniques of rating mucositis. In addition, relatively few clinical trials have focused on mucositis as a specific outcome. Currently, the only effective preventive strategies include the use of palifermin to prevent OM in the setting of hematopoietic stem cell transplantation and oral cryotherapy used in conjunction with bolus 5-FU, melphalan, or edatrexate. For the most part, managing OM relies on supportive care and symptom palliation. However, OM is a common problem associated with significant patient morbidity and increased resource use. The magnitude of the problem demands innovative approaches based on expert judgment as evidence accumulates to support specific recommendations. To improve this situation, the NCCN convened a multidisciplinary task force to address key issues. This report integrates expert judgment with a review of key literature on risk assessment, prevention, and treatment strategies, and provides recommendations for the overall management of OM.