Although cytology-based cervical cancer prevention programs have reduced the incidence of cervical cancer in many industrialized countries, the limited sensitivity of cervical cytology makes these programs difficult and expensive to maintain. Therefore, over the next several years it is likely that we will begin to switch from cervical cytology-based screening programs to programs based on testing for high-risk types of human papillomavirus (HPV). Multiple large, well-controlled screening trials have clearly demonstrated that HPV testing is considerably more sensitive than cytology (either conventional or liquid-based) and only slightly less specific when used in women 30 years of age and older. Initially, we will use a combination of cervical cytology and HPV testing to screen, but as more data from large screening studies become available, it is becoming clear that cytology provides little benefit over using HPV testing alone to screen. Therefore, in the future it is likely that we will use HPV testing alone to screen, and reserve cervical cytology as a way to determine which HPV-positive women require additional follow-up or colposcopy.