Over the past several decades, knowledge of the biology and epidemiology of human papillomavirus (HPV) infection has increased tremendously. However, there are still many unanswered questions concerning the interaction of the virus with its host. The virus has been identified as a necessary causal agent for cervical squamous neoplasia and has been linked to the development of neoplasia in several other mucosal sites. The viral oncogenes E6 and E7 are the major players in the virus' scheme to evade the immune system and use the host cell replication machinery to survive. Many risk factors for infection with HPV have been identified; however, the focus now centers on identifying risk factors for persistence of the infection as it is likely that transient infections play a very small role in the overall development of clinical disease. Prevention measures to date have centered around screening programs, mostly for cervical cancer, including the perfection of screening techniques and inclusion of molecular testing for HPV into screening regimens. The development of prophylactic and therapeutic vaccines has also increased as primary prevention measures appear to have the best hope for long-term effects on cancer incidence.