Cervical cancer is one of the most common neoplastic diseases affecting women, with a combined worldwide incidence of almost half a million new cases annually, second only to breast cancer. Basic and epidemiologic research conducted during the past 15–20 years have provided overwhelming evidence for an etiologic role for infection with certain types of sexually-transmitted human papillomavirus (HPV) as the primary cause of cervical cancer. The relative risks of cervical cancer following HPV infection as ascertained in case-control and cohort studies are among the highest in cancer epidemiology. The available evidence indicates that the HPV-cervical cancer association satisfies all relevant causal criteria for public health action. Other cervical cancer risk factors, such as smoking, parity, use of oral contraceptives, diet, other infections, and host susceptibility traits must be understood in the context of mediation of acquisition of HPV infection or in influencing events of the natural history of cervical neoplasia that occur following the establishment of a persistent HPV infection. Virtually all cervical carcinoma specimens contain HPV DNA, which suggests that HPV infection is a necessary cause of cervical neoplasia. This is the first instance in which a necessary cause has been demonstrated in cancer epidemiology—a realization that has obvious implications for primary and secondary prevention of this neoplastic disease.