Mycoplasma pneumoniae is a pathogenic mycoplasma responsible for respiratory tract infections in humans, which occurs worldwide in children and adults. This article focuses on its antibiotic susceptibility profile and on the development of acquired resistance in this microorganism. The lack of a cell wall in mycoplasmas makes them intrinsically resistant to β-lactams and to all antimicrobials that target the cell wall. M. pneumoniae is susceptible to macrolides and related antibiotics, tetracyclines and fluoroquinolones. Macrolides and related antibiotics are the first-line treatment for respiratory infections caused by M. pneumoniae. However, strains with acquired resistance to macrolides have recently emerged worldwide and have been spreading in Europe, USA and A sia especially, with more than 90% of Chinese isolates resistant to erythromycin and azithromycin. This acquired resistance can be detected by PCR methods directly from respiratory specimens and is related to 23S rRNA mutations.