Chlamydia are ancient and successful pathogens, evolutionary distinct from most bacteria and highly adapted to an intracellular lifestyle. To propagate, Chlamydia deploy a plethora of resources oriented to fulfill different steps of their pathogenic strategy, including infection and invasion of their host cells, the transition from infectious elementary bodies to replicative reticulate bodies, establishing an intracellular replicative niche inside a membrane-enclosed compartment (the “inclusion”), transition back to elementary bodies and finally, exit of the host cell. Each of these steps involves complex and poorly understood interactions with their hosts.

As obligate intracellular pathogens, Chlamydia have evolved many strategies to acquire nutrients and manipulate cell pathways to evade the anti-bacterial responses elicited by the host. Technical advances in imaging, high-throughput “omics”, sequencing, and genetic tools have contributed to unraveling some of the chlamydial adaptive mechanisms and virulence factors. The ability to manipulate the chlamydial genome, which has been an unreachable challenge until only a few years ago, opened the door to elucidate, at the molecular level, the chlamydial factors relevant for the intracellular lifestyle, the pathogenic mechanisms, and immune evasion that these bacteria use to establish acute or persistent infections. Discovering how Chlamydia exploit host cell signaling, vesicular transport, and metabolism will help to unravel obligate intracellular bacterial survival mechanisms. Gathering recent breakthroughs in Chlamydia biology, pathogenesis, interactions with host cells, strategies for intracellular survival, persistence, and bacterial mechanism for immune response evasion constitutes a key platform for developing novel preventive and therapeutic anti-chlamydial approaches, including vaccines. A detailed assessment of bacterial proteins, effectors and enzymes involved in any step of Chlamydia development (cell invasion, inclusion development, replication and exit from host cells) is crucial for understanding the rampant success of Chlamydia intracellular lifestyle. Moreover, the characterization of Chlamydia persistence is critical for expanding current information about chronic infections and relapse after treatment. In this context,