The papillomaviruses (PVs) are a large family of DNA viruses indigenous to many, if not all, vertebrate species. The unique feature of these viruses is that they all induce primarily benign proliferations of epithelial cells in their natural hosts. Individual members of this family show a high degree of both species specificity and tissue specificity. Squamous or mucosal epithelial cells are the targets of infection. The life cycle of the virus is intimately coupled to the differentiation program of infected tissue. Conversely, expression of the early viral genes interferes with the normal pattern of keratin expression, cell cycle regulation, and terminal differentiation, which ultimately gives rise to aberrant cells. With some viral types, however, these benign proliferations progress into aggressive malignancies.