Many studies have evaluated selective screening criteria for women in various settings. Most have concluded and all guidelines recommend that all women aged < 25 be screened yearly for C. trachomatis infection. Behavioral criteria, such as the number of sex partners, new or more than one sex partners, and previous infection, also can serve as criteria for screening women aged > 25. Because re-infection rates are high and occur within a few months, complications may be reduced further if partners are treated and women rescreened 4 to 6 months after initial infection. Revised recommendations for C. trachomatis screening programs have stated that more frequent screening may be considered among women < 20 and those with recent infection. Screening in nontraditional settings and careful evaluation of local prevalence and risk factor information should be encouraged. Private providers and emergency room providers should discuss screening recommendations and adopt a C. trachomatis screening policy for the population they serve. The HEDIS measure should serve to encourage at least annual screening of 15- to 25-year-old sexually active females through providers linked to managed care organizations. In general, high yields (ie, percentage of tests that are positive) in nontraditional settings and enhanced feasibility and acceptability of urine-based tests may encourage further innovative approaches to reach and screen populations at risk. Several issues remain to be addressed to increase the effectiveness of screening efforts. If more sensitive amplification tests are used widely, more infected persons will be identified and treated, and transmission patterns may change, particularly if partner treatment also occurs. Current screening criteria should continue to be re-evaluated. An important issue that affects testing methods includes the possible need for confirmation testing when using NAATs if the prevalence of C. trachomatis is less than 2%. If the sensitivity of an NAAT is 85% and specificity is 99%, in a hypothetical population of 10,000 with a prevalence of 2%, the positive predictive value is 170/268 (63%). A second important issue affecting testing methods and feasibility of using NAATs for screening large numbers of individuals is the pooling of urine specimens, which has been evaluated in several studies and found to be very effective for reducing costs. A research issue for pooling is the determination of the most cost-effective prevalence levels for pooling. An additional research question is in which populations should a NAAT be used for detection of C. trachomatis and N. gonorrhoeae. There are no recommendations for the routine screening of men because of the paucity of data showing that this strategy can reduce sequelae. The CDC is conducting a multisite study to examine the feasibility, acceptability, and usefulness of screening of asymptomatic men. There are a few studies have determining cost-effective prevalence threshold levels, particularly with NAATs. A recently developed decision analysis model by CDC designed to maximize the effectiveness of screening strategies for C. trachomatis infections may be useful for decision makers. It is intended to serve as an easy and flexible tool to determine cost effectiveness at a local level and takes into account positivity rates and test performance characteristics (SOCRATES). It is unclear if recurrent infection is caused by true re-infection by the same or a different partner or recurrence of initial infection. Recurrence may be caused by persistence of C. trachomatis or antibiotic resistance. This distinction is of scientific interest because the appropriate intervention differs (eg, identification of risk factors for the former and microbiologic investigations for the latter). Effective partner management and retesting are critical to reducing sequelae of C. trachomatis infection. Screening for C. trachomatis infection remains an essential component of C. trachomatis control. It is cost effective, most infections are asymptomatic, and symptom-based health care seeking and testing identify few of those infected. The likelihood that opportunities for screening are missed is high particularly in non-STD clinic settings. Local studies using NAATs to determine C. trachomatis prevalence and risk factors are helpful to health care providers so they can make evidence-based decisions on who to screen. The use of nontraditional, non-clinic-based test settings should be explored further. We have focused on summarizing the medical evidence regarding recommendations for screening for C. trachomatis. High-risk populations for C. trachomatis infection may overlap with populations for other STDs, and comprehensive STD prevention programs that involve a range of STD service providers are needed to successfully reduce the STD-related health burden in the population.