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Head and neck cancers are a common spectrum of diseases, accounting for over one-third of a million deaths worldwide each year, and over 11,000 annual US deaths. Most head and neck cancers have traditionally been diagnosed in older males who abuse tobacco and/or alcohol. With increasing public awareness of the dangers of tobacco exposure and excessive alcohol intake, the incidence of many subgroups of head and neck cancer is now decreasing in the West. However, over the past several decades, the rates of carcinomas of the tonsil and base of tongue are increasing, and are affecting a different demographic group consisting mainly of younger, nonsmoking, males. These lesions are caused by infections with the same high-risk human papillomaviruses (HPV) genotypes as those responsible for cervical cancer and other anogenital neoplasms. These HPV-induced head and neck cancers differ in their biology and prognosis from those neoplasms induced by tobacco or ethanol. Understanding the biology of these lesions will allow for the development of selective preventive and treatment strategies, and better outcomes, for this subpopulation of patients.