This article reviews the data available as of 2004 on the effectiveness and cost-effectiveness of cervical screening with the two available cytologic methods, the conventional Papanicolaou (Pap; CP) smear and liquid-based cytology (LBC), and discusses the application of LBC to current practice. The majority of LBC studies are on the ThinPrep Pap Test (CYTYC, Boxsborough, MA) and the remainder are on SurePath (TriPath, Burlington, NC), which was previously known as AutoCyte Prep. LBC identified more low-grade squamous intraepithelial lesion (LSIL) Pap test results compared with paired conventional cytology in 17 of 21 ThinPrep and 9 of 12 SurePath “split-sample” studies considered to fulfill the criteria for inclusion in the British NHS Health Technology Assessment (HTA) evaluation of cervical cytology. In four of the six recent ThinPrep and one of two SurePath split-sample studies, more high-grade squamous intraepithelial lesion-positive (HSIL+) results were identified by LBC than by CP. All 15 “direct-to vial studies” meeting HTA criteria reported more LSIL+ results for LBC compared with CP, and all eight of the direct-to-vial studies reporting HSIL+ results separately showed increased detection of high-grade cytology interpretations. Fifteen studies met the criteria for evaluating sensitivity and specificity. Aggregate sensitivity for the CP was 71.5% and for LBC was 80.1%. Indirect comparisons of the two LBC methods did not detect a difference in sensitivity, and a meta-analysis of the six studies comparing specificity between CP and LBC found no difference. Other capabilities of LBC are improved specimen adequacy and the ability to do ancillary testing out of the liquid-based vial. In cost-effective analyses based on models of disease natural history and/or the clinical effectiveness of each screening modality, screening with CP was always dominated by screening with LBC. Primary cervical screening guidelines issued by the American Cancer Society in 2002 recommend repeating the cytology biannually if liquid-based and annually if conventional. The gain in sensitivity, apparent cost-effectiveness, and advantage of having a representative specimen for ancillary testing, support the use of LBC.