Sexually transmitted Chlamydia trachomatis infection is an important public health concern with major adverse effects on female reproductive tract health and function. The magnitude of reproductive morbidity associated with sexually transmitted C. trachomatis infection is enormous, however to date no prophylactic vaccine is available. In part this is due to the lack of information on the mucosal immunobiology of the host-pathogen interaction and correlates of protective immunity during genital C. trachomatis infection. In this review, we focus on current knowledge of mucosal innate and adaptive immune responses in the female genital tract during C. trachomatis infection, which will eventually help in the development of a vaccine for prevention of chlamydial infection.