Genital infection with Chlamydia trachomatis is an escalating global public health concern causing considerable morbidity and socioeconomic burden worldwide. Although antibiotics are used to treat symptomatic urogenital infections, chlamydial infection remains asymptomatic in approximately 50% of infected men and 70% of infected women. The major clinical manifestations of genital chlamydial infection in women include mucopurulent cervicitis, endometritis and pelvic inflammatory disease. Genital infection with C. trachomatis markedly enhances the risk for reproductive tract sequelae in women, including tubal factor infertility, chronic pain and ectopic pregnancy. Definitive infection control of chlamydial infections will likely be achievable through a safe and efficacious vaccine. This will require identifying protective chlamydial antigens in animal models as well as identifying effective adjuvants and delivery systems that target subunit vaccines to immune inductive sites or secondary lymphoid tissues, and will be safe for use in humans.