The anogenital human papillomavirus (HPV) is estimated to be the most commonly occurring sexually transmitted infection in the US. Comprehensive estimates of the annual economic burden associated with the prevention and treatment of anogenital HPV-related disease in the US population are currently unavailable. The purpose of this paper is to (i) outline an analytic framework from which to estimate the annual economic burden of preventing and treating anogenital HPV-related disease in the US; (ii) review available US literature concerning the annual economic burden of HPV; and (iii) highlight gaps in current knowledge where further study is particularly warranted. Among eight US studies identified that describe the annual economic burden pertaining to one or more aspects of anogenital HPV-related disease, three met the review eligibility criteria (published between 1990 and 2004, examined multiple facets of annual anogenital HPV-related economic burden, and clearly articulated the data and methods used in the estimation process). All costs were adjusted to 2004 US dollars. Estimates of the annual direct medical costs associated with cervical cancer were comparable across studies (range 300-400 million US dollars). In contrast, there was a wide range across studies for estimates of the annual direct medical costs associated with cervical intraepithelial neoplasia (range 700 million US dollars-2.3 billion US dollars). Only one study reported direct medical costs for anogenital warts (200 million US dollars) and routine cervical cancer screening (2.3 billion US dollars). No studies examined direct medical costs attributable to HPV-related anal, penile, vaginal or vulvar cancers, or the work and productivity losses resulting from time spent receiving medical care, morbidity or mortality. Current economic burden estimates would suggest annual direct medical costs associated with the prevention and treatment of anogenital warts and cervical HPV-related disease of at least 4 billion US dollars. This figure would likely rise to at least 5 billion US dollars per year if direct medical costs associated with other disease entities caused by the sexual transmission of HPV were included, with further additions to the economic burden totalling in the billions of dollars if work and productivity losses were incorporated, a research priority for future studies.