The biological history of Chlamydia trachomatis is intertwined with the evolution of the man. Infecting Elemental Bodies (EBs), having penetrated mucosal epithelial cells, wrap themselves in a cloak (ĸλαμις) of glycogen that ensures their obligatory intracellular survival and protects this differentiation into Reticulate Bodies (RBs) that feed on cellular ATP. Multiple chemokines and cytokines are involved under the direction of IL-6 in the florid phase and IL-17A in the scar phase. The WHO has successfully identified the SAFE strategy against trachoma (Surgery, Antibiotics, Facial cleansing, Environment) as the blueprint to eliminate the disease by 2020. Recently, interest has been increasingly focused on changing sexual attitudes in different areas of the world, leaving Musca sorbens, Scatophaga stercoraria, and stepsisters fairly blameless, but extolling the role of Chlamydia trachomatis in apparently “sterile” chronic prostatitis or conjunctivitis or, less frequently, in oropharyngitis and proctitis. The addition of an S (SAFE-S) standing for “sexual behavior” was then proposed to also attract the interest and attention not only of Ophthalmologists and Obstetricians/Gynecologists, Urologists/Andrologists, and the School Authorities for information on the prevention of sexually transmitted diseases, but also of Social Physicians and Pediatricians. This means that sexually transmitted infections should be screened in asymptomatic patients with risky sexual behavior or sexual contact with people diagnosed with a transmitted infection.