Infections caused by microorganisms of the Chlamydiaceae family are widespread among people and animals all over the world. Recently, however, an increased number of reports has been noted that point to the inefficacy of treatment with antibiotics known until now as a “first choice” solution. Resistance to antibiotics in Chlamydiaceae is defined as phenotypic resistance, but it may result from heterotypic resistance. As far as antimicrobial resistance is concerned, genomic islands and efflux pump mechanism may also play a role in its development. Only few laboratories have the capacity for the culture of progeny strains and the assessment of their resistance to antibiotics. Therefore, the resistance of field strains to chemotherapeutics usually remains unrecognized, and the drugs applied may prove inefficacious.