Chlamydia trachomatis is an obligate intracellular pathogen with approximately 131 million cases of sexually transmitted infection each year. The infection can result in serious sequelae such as pelvic inflammatory disease, infertility, or ectopic pregnancy. Recently, using a cohort study design the investigators on the Australian Chlamydia Treatment Study have identified that more women then originally thought fail to resolve the infection after treatment with azithromycin. The isolates have been cultured and characterised and after culture no evidence of a higher MIC to azithromycin was detected. However, sequence capture analysis and immediate culture in the presence of azithromycin from the swab suggests that the in vivo chlamydial population is more dynamic and distinct than what we can culture in the laboratory. The possible role of chlamydial persistence, specific genomic loci in members of the population and population dynamics all appear to differ in the Chlamydia from the women who failed treatment compared to women who resolved the infection after azithromycin treatment. Here, we will present the first genomic analysis of chlamydia in women who failed treatment, and the first characterisation of persistence and growth phenotypes of isolates associated with treatment failure and present our model for how treatment failure occurs in Chlamydia.