Despite the fact that cervical cytology screening programs have dramatically reduced the prevalence of cervical cancer in the US, women continue to develop and die from the disease. The most important observation contributing to this failing is that 60% of women with invasive cancer have not had a Pap smear in the previous 5 years (or have never had one). The most clinically effective and cost effective approach to reducing the incidence of cervical cancer is to screen the unscreened population. Recent evidence has also noted that the sensitivity of conventional cytology is also much lower than was previously believed. Much recent investigation has been directed at identifying the reasons for this low sensitivity and identifying ways to improve it. Only by improving the sensitivity of cervical cancer screening and participation in screening programs can the prevalence, morbidity, and mortality from cervical cancer be further reduced.