The "silent epidemic" of Chlamydia trachomatis threatens to cause reproductive damage and infertility in many of the 50 million women who acquire it each year. Female reproductive tract infection has more recently been linked to stillbirth and premature delivery. Innate immune cells and mediators appear to be the primary players in pathogenesis, with neutrophils playing a prominent role in disease development. Although adaptive antibody and CD4 T cell responses appear primarily protective, these responses are inefficient. Infections are frequently chronic as a result, and when infection is diagnosed and treated with appropriate antibiotics, repeated infection is the rule. The lack of acute symptoms in many infected individuals contributes to the high prevalence of chlamydial infection. Although chronic sequelae are relatively rare in men, and many women sustain infection without developing pelvic inflammatory disease or chronic sequelae, the extremely high prevalence of chlamydial infection leads to significant morbidity and healthcare costs. A vaccine is urgently needed to prevent infection, but given the difficulties of inducing a CD4 T cell memory response that can home quickly to the genital tract, induction of sterilizing immunity may not be possible. A vaccine that prevents disease by lowering bacterial burden and dampening production of tissue-damaging responses may be possible. Until an efficacious vaccine is developed, screening and treatment programs appear to be the best method of disease prevention.