Mass vaccination against human papillomavirus (HPV) genotypes 16 and 18 will, in the long term, reduce the incidence of cervical cancer, but screening will remain an important cancer control measure in both vaccinated and unvaccinated women. Since the 1960s, cytology screening has helped to reduce the incidence of cervical cancer, but has a low sensitivity for high-grade cervical intraepithelial neoplasia (CIN) and requires frequent testing. Several HPV tests have become available commercially. They appear to be more sensitive for high-grade CIN, and may further reduce the incidence of cervical cancer compared with cytology. However, they are associated with an increased frequency of positive tests without underlying CIN, and therefore increase the need for colposcopy and repeated testing. This problem will pose a major challenge for switching from cytology-based to HPV-based screening. The aim of this article is to discuss the role and the use of HPV tests and HPV genotyping in unvaccinated women.