Human papillomaviruses (HPVs) are a family of small double-stranded DNA viruses that have a tropism for the epithelia of the genital and upper respiratory tracts and for the skin. Approximately 150 HPV types have been discovered so far, which are classified into several genera based on their DNA sequence. Approximately 15 high-risk mucosal HPV types are clearly associated with cervical cancer; HPV16 and HPV18 are the most carcinogenic since they are responsible for approximately 50% and 20% of all cervical cancers worldwide, respectively. It is now also clear that these viruses are linked to a subset of other genital cancers, as well as head and neck cancers. Due to their high level of carcinogenic activity, HPV16 and HPV18 are the most studied HPV types so far. Biological studies have highlighted the key roles in cellular transformation of the products of two viral early genes, E6 and E7. Many of the mechanisms of E6 and E7 in subverting the regulation of fundamental cellular events have been fully characterized, contributing not only to our knowledge of how the oncogenic viruses promote cancer development but also to our understanding of basic cell biology. Despite HPV research resulting in extraordinary achievements in the last four decades, significantly improving the screening and prophylaxis of HPV-induced lesions, additional research is necessary to characterize the biology and epidemiology of the vast number of HPV types that have been poorly investigated so far, with a final aim of clarifying their potential roles in other human diseases.