Chlamydial infections lead to a number of clinically relevant diseases and induce significant morbidity in human populations. It is generally understood that certain components of the host immune response to infection also mediate such disease pathologies. A clear understanding of pathogenic mechanisms will enable us to devise better preventive and/or intervention strategies to mitigate the morbidity caused by these infections. Over the years, numerous studies have been conducted to explore the immunopathogenic mechanisms of Chlamydia-induced diseases of the eye, reproductive tract, respiratory tract, and cardiovascular systems. In this article, we provide an overview of the diseases caused by Chlamydia, animal models used to study disease pathology, and a historical context to the efforts to understand chlamydial pathogenesis. Furthermore, we discuss recent findings regarding pathogenesis, with an emphasis on the role of the adaptive immune response in the development of chlamydial disease sequelae. Finally, we summarize the key insights obtained from studies of chlamydial pathogenesis and avenues that remain to be explored in order to inform the next steps of vaccine development against chlamydial infections.