Infection with human papillomaviruses (HPVs) is a major public health burden worldwide and is associated with benign and malignant lesions of the skin and genital tract. HPV causes cervical cancer, which represents the second most prevalent cancer in women worldwide. Functions of the viral oncogenes E6 and E7 are essential for carcinogenesis and for support of the viral life cycle. We will begin by discussing the relationship between HPV infection and disease, followed by a review of E6 and E7 activities and their respective cellular targets. Particular emphasis will be placed on established and newly discovered mechanisms by which E7 inhibits members of the cellular retinoblastoma protein family. We will then describe how current research links the above molecular interactions to malignant transformation as well as to aspects of the viral life cycle in vitro and in vivo. As a result of decades of intense HPV research, promising therapies to prevent infection and to treat HPV associated cancers are now on the horizon. We will conclude our review by a description of potential gene therapeutic and hormonal approaches and of new developments in the design of effective vaccines.