Over 100 human papillomavirus (HPV) types have been identified to date, of which over 40 infect the genital tract, primarily through sexual transmission. The many different genital HPV types appear to infect, resolve, or persist, and cause abnormal cytology and cervical intraepithelial neoplasia. Several cofactors have been associated with HPV persistence and lesion progression, including smoking, long-term oral contraceptive use, other sexually transmitted infections, host immunogenetics, and viral factors, such as HPV type and HPV variants. Given the discovery of HPV as the single primary cause of invasive cervical cancer, primary and secondary interventions have been realized, including HPV testing in cervical screening programs and prophylactic HPV vaccines. Because first generation HPV vaccines only target the two most common HPV types found in cervical cancer (HPV 16 and 18), cervical screening programs must continue, and the relative roles of HPV vaccination in young women and HPV testing in older women (alone or in conjunction with cytology) will be determined over the next decades.