Molecular and epidemiological studies conducted over the last 20 years led to the recognition of certain types of human papillomavirus (HPV) as the etiological agents of cervical cancer, a very common neoplasia, particularly in developing countries. More than 70 HPVs have been described, including both cutaneous and mucosal types. About half of the known HPVs, and an even higher number of variants, have been isolated from genital mucosas. The association of certain types primarily with normal tissues and benign lesions, as opposed to cancer-associated types, has led to the concept of low and high oncogenic risk HPVs, respectively. The latter express oncogenic proteins that interfere with cell growth control functions. As a consequence of the continuous expression of these viral genomes, chromosome instability may occur, leading to fully transformed cells. Studies indicate that persistence of high-risk HPVs may determine progression to more severe stages of cervical disease, while the majority of HPV infections are transient and do not seem to be important in cervical carcinogenesis. The risk for disease progression seems also to be associated with viral burden. Prospective epidemiological studies will contribute to the knowledge of the natural history of HPV infections and provide information on the determinants of viral persistence. Data derived from these studies may define the clinical utility of HPV testing and its use in cervical cancer prevention programs.