Chlamydia trachomatis continues to be the most commonly reported sexually transmitted bacterial infec-tion in many countries with more than 100 million new cases estimated annually. These acute infectionstranslate into significant downstream health care costs, particularly for women, where complicationscan include pelvic inflammatory disease and other disease sequelae such as tubal factor infertility.Despite years of research, the immunological mechanisms responsible for protective immunity versusimmunopathology are still not well understood, although it is widely accepted that T cell driven IFN-gand Th17 responses are critical for clearing infection. While antibodies are able to neutralize infectionsin vitro, alone they are not protective, indicating that any successful vaccine will need to elicit botharms of the immune response. In recent years, there has been an expansion in the number and types ofantigens that have been evaluated as vaccines, and combined with the new array of mucosal adjuvants,this aspect of chlamydial vaccinology is showing promise. Most recently, the opportunities to developsuccessful vaccines have been given a significant boost with the development of a genetic transformationsystem for Chlamydia, as well as the identification of the key role of the chlamydial plasmid in virulence.While still remaining a major challenge, the development of a successful C. trachomatis vaccine is startingto look more likely.