Human papillomaviruses (HPVs) have been recognized as the main etiologic agent of cervical cancer and other anogenital neoplasms, and a leading cause of death from cancer worldwide. In the last twenty years, extensive research has contributed to document the molecular mechanisms of virus persistence and malignant transformation, confirming a direct role of viral proteins in these processes. A clear understanding of the molecular epidemiology of HPVs and the availability of powerful molecular diagnostic techniques have provided the background for prevention strategies of HPV-related carcinomas. Since these viruses are highly prevalent in the general population, strict screening programs are still necessary. Recently, major breakthroughs have emerged from immunological studies. Indeed, these studies have paved the way for medical treatment of HPV infections and provided the first highly effective preventive vaccines. For these principal reasons, the time has come for a great effort towards the eradication of these important human pathogens. The present review summarizes the main aspects of the virology, molecular epidemiology and molecular biology of HPV infection and highlights the recent perspectives of prevention and treatment of the HPV-related disease.