Chlamydia trachomatis is an important cause of sexually transmitted infection that can manifest as acute cervicitis, pelvic inflammatory disease, and most commonly, chronic asymptomatic infection. The basis of this wide spectrum of manifestations and the factors that lead to clearance or chronic infection are poorly understood. We reviewed specific literature pertaining to clearance of primary genital tract infections in animal models, including mice, guinea pigs, pigs, sheep, and nonhuman primates. T helper 1 cell responses involved in cell-mediated immunity are key immune parameters that define efficient clearance in the murine and guinea pig models of chlamydial infection, which are useful for studying C. trachomatis clearance. However, there may be some differences between humans and other animals in innate and adaptive immune responses to chlamydial infection. Studies have suggested that differences in the induced T cell subsets and the species-specific differences in interferon gamma-mediated effector mechanisms may play a significant role in these discrepancies. To close these gaps in knowledge, translational research in humans is a critical next step. However, for questions about specific mechanisms of host-pathogen interaction that cannot be answered feasibly or ethically in humans, animal models will continue to be important. Future research should include use of humanized and nonmurine models that establish prolonged infection to improve understanding of chronic human infections.