The plethora of ocular, genital and respiratory diseases of Chlamydia, including nongonococcal urethritis, cervicitis pelvic inflammatory disease, ectopic pregnancy, tubal factor infertility, conjunctivitis, blinding trachoma and interstitial pneumonia, and chronic diseases that may include atherosclerosis, multiple sclerosis, adult onset asthma and Alzheimer's disease, still pose a considerable public health challenge to many nations. Although antibiotics are effective against Chlamydia when effectively diagnosed, asymptomatic infections are rampart, making clinical presentation of complications often the first evidence of an infection. Consequently, the current medical opinion is that an effective prophylactic vaccine would constitute the best approach to protect the human population from the most severe consequences of these infections. Clinical and experimental studies have demonstration that Chlamydia immunity in animals and humans is mediated by T cells and a complementary antibody response, and the completion of the genome sequencing of several isolates of Chlamydia is broadening our knowledge of the immunogenic antigens with potential vaccine value. Thus, major advances have been made in defining the essential elements of a potentially effective subunit vaccine design and parameters for evaluation. However, the challenge to develop effective delivery systems and human compatible adjuvants that would boost the immune response to achieve long-lasting protective immunity remains an elusive objective in chlamydial vaccine research. In response to evolving molecular and cellular technologies and novel vaccinology approaches, considerable progress is being made in the construction of novel delivery systems, such as DNA and plasmid expression systems, viral vectors, living and nonliving bacterial delivery systems, the use of chemical adjuvants, lipoprotein constructs and the codelivery of vaccines and specific immuno-modulatory biological agonists targeting receptors for chemokines, Toll-like receptors, and costimulatory molecules. The application of these novel delivery strategies to Chlamydia vaccine design could culminate in timely achievement of an efficacious vaccine.