Xerostomia is a common, debilitating complication of radiation therapy (RT) for head and neck cancer. This article reviews the pathogenesis of radiation-induced xerostomia, its impact on quality of life (QOL), and treatment options. Virtually all patients undergoing RT for head and neck cancers have xerostomia, which causes oral discomfort and pain, increased dental caries and oral infection, and difficulty speaking and swallowing. This significantly impairs QOL and can compromise nutritional intake and continuity of cancer therapy. The literature describing pathogenesis, impact on QOL of radiation-induced xerostomia, and preventive and interventional therapies was reviewed. Current management strategies include stringent dental and oral hygiene; parotid-sparing radiation techniques to prevent or minimize xerostomia; and pharmacotherapies, such as salivary substitutes and sialogogues. Future strategies may include advanced three-dimensional intensity-modulated RT techniques, salivary gland transfer, newer sialogogues, and gene therapy. New treatment approaches to xerostomia from RT for head and neck cancer may result in significant improvement in patient QOL. Copyright 2004 Wiley Periodicals, Inc.