**Abstract**

*Chlamydia spp.* are important causes of acute and persistent/chronic infections. All *Chlamydia spp*. display a unique biphasic developmental cycle alternating between an infectious elementary body (EB) and a replicative form, the reticulate body (RB), followed by the multiplication of RBs by binary fission and progressive differentiation back into EBs. During its intracellular life, *Chlamydia* employs multiple mechanisms to ensure its persistence inside the host. These include evasion of diverse innate immune responses, modulation of host cell structure and endocytosis, inhibition of apoptosis, activation of pro-signaling pathways, and conversion to enlarged, non-replicative but viable "aberrant bodies" (ABs). Early research described several systems for Chlamydial persistence with a significant number of variables that make a direct comparison of results difficult. Now, emerging tools for genetic manipulations in *Chlamydia* and advances in global microarray, transcriptomics, and proteomics have opened new and exciting opportunities to understand the persistent state of *Chlamydia* and link the immune and molecular events of persistence with the pathogenesis of recurrent and chronic Chlamydial infections. This chapter reviews our current understanding and advances in the molecular biology of *Chlamydia* persistence.

**Keywords:** *Chlamydia* persistence, elementary bodies (EBs), reticulate bodies (RBs), aberrant bodies (ABs), inclusion, inhibition of apoptosis, non-coding RNAs, pro-survival pathways, genome-scale analyses, interference innate immune system
