Chlamydia trachomatis infections are the most common bacterial sexually transmitted disease in the United States. A substantial proportion of initial infections in both men and women are asymptomatic. Use of nucleic acid amplification-based diagnostic tests on first-void urine makes it possible to initiate community-based screening programs aimed at identifying asymptomatically infected men and women. Directly observed single-dose therapy with azithromycin is now available. Screening programs have been demonstrated to reduce the overall prevalence of chlamydial infection in the tested population and to reduce the incidence of subsequent pelvic inflammatory disease in previously screened women. The sequelae of chlamydial infections are likely due to immunopathologically mediated events in which both the chlamydial 60 kDa heat-shock protein and genetic predisposition of specific patients play a role. An improved understanding of immunologic events leading to upper genital tract scarring is needed to target specific interventions and facilitate development of a vaccine.