Pterygium is a potentially vision-threatening fibrovascular lesion originating from the conjunctiva that often extends on the corneal surface. Although it has been extensively studied, its pathogenesis has yet to be fully elucidated. Recent evidence on molecular genetic abnormalities in pterygium suggested neoplastic changes of limbal stem cells potentially associated with exposure to ultraviolet (UV) light. Human papillomavirus (HPV) is an oncogenic virus, associated with squamo-proliferative lesions of the anogenital region, skin and oropharynx. Several studies have shown HPV involvement in the pathogenesis of conjunctival neoplastic lesions, including papilloma and squamous cell carcinoma. The involvement of HPV as a co-factor in the pathogenesis of pterygium, although suggested by several studies using PCR and immunohistochemical techniques, remains controversial. Moreover, a marked variation in the prevalence of HPV in ophthalmic pterygium has been reported by different studies. Ethnic susceptibility and methodological differences in the detection of HPV may account for this variation. Surgical excision, often using sophisticated techniques, is the standard current method of therapy for pterygium. However, recurrences are frequent and recurrent lesions tend to be more aggressive. If indeed HPV is involved in pterygium pathogenesis or recurrence, anti-viral medications or vaccination may be new options in pterygium therapy.