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Of particular interest is the discovery that glutamate receptor reactive reagents can influence tumor biology. However, the knowledge of glutamate signaling in peripheral tissues is still incomplete and, in the case of head and neck areas, is almost lacking. The roles of glutamate signaling pathways in these regions are manifold and include orofacial pain, periodontal bone production, skin and airway inflammation, as well as salivation. Furthermore, the interrelations between glutamate and cancers in the oral cavity, thyroid gland, and other regions are discussed. In summary, this review shall strengthen the view that glutamate receptor reagents may also be promising targets for novel therapeutic concepts suitable for a number of diseases in peripheral tissues. The contents of this review cover the following sections: Introduction; The \u201cGlutamate System\u201d; The Taste of Glutamate; Glutamate Signaling in Dental Regions; Glutamate Signaling in Head and Neck Areas; Glutamate Signaling in Head and Neck Cancer; A Brief Overview of Glutamate Signaling in Other Cancers; and Conclusion. \u00a9 2010 Wiley Periodicals, Inc. 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