Oropharyngeal mucositis is a common and treatment-limiting side effect of cancer therapy. Severe oral mucositis can lead to the need to interrupt or discontinue cancer therapy and thus may have an impact on cure of the primary disease. Mucositis may also increase the risk of local and systemic infection and significantly affects quality of life and cost of care. Current care of patients with mucositis is essentially palliative and includes appropriate oral hygiene, nonirritating diet and oral care products, topical palliative mouth rinses, topical anesthetics, and opioid analgesics. Systemic analgesics are the mainstay of pain management. Topical approaches to pain management are under investigation. The literature supports use of benzydamine for prophylaxis of mucositis caused by conventional fractionationated head and neck radiotherapy, and cryotherapy for short-half-life stomatoxic chemotherapy, such as bolus fluorouracil. Continuing studies are investigating the potential use of biologic response modifiers and growth factors, including topical and systemic delivery of epithelial growth factors and agents. Progress in the prevention and management of mucositis will improve quality of life, reduce cost of care, and facilitate completion of more intensive cancer chemotherapy and radiotherapy protocols. In addition, improved management of mucositis may allow implementation of cancer treatment protocols that are currently excessively mucotoxic but may produce higher cure rates. Continuing research related to the pathogenesis and management of mucositis will undoubtedly lead to the development of potential interventions and improved patient care.