Human papillomaviruses (HPV) are small DNA viruses associated with specific mucosal and epithelial lesions ranging from benign proliferative lesions to invasive carcinomas. Over 100 types of HPV have been identified, some of which are associated with benign lesions (low risk types) and others are associated with malignancies (high risk types). While the genome consists of 6 early genes and 2 late genes, the E6 and E7 genes have been most studied because they interact with p53 and Rb, respectively, thus contributing to the ability of HPV to mediate oncogenesis. Cervical carcinoma is the most common and most studied HPV-related malignancy. These lesions are thought to be originated from persistent high-risk type HPV infections which progress to well characterized precursor lesions and finally to carcinoma. This same HPV related progression has also been observed in other anogenital malignancies including anal, penile and vulvar carcinomas. Although the evidence is not as conclusive, HPV also likely plays a role in the development of a subset of squamous cell carcinomas of the head and neck as well as other cutaneous malignancies. While HPV infection is common, the progression to malignancy is relatively rare indicating a potential role for immune protection against persistent infection. This is supported by the fact that HPV infection and related malignancies are common in the immunosuppressed population. Thus, efforts have been placed on development of HPV vaccines to prevent and treat these common and diverse groups of HPV related malignancies.