Abstract: Mycoplasma pneumoniae is a major pathogen responsible for respiratory infections in children. In recent years, the incidence of clinical infection caused by macrolide-resistant M. pneumoniae increased obviously, the infection is characterized by prolonged fever duration, higher incidence of extrapulmonary complication, increased hormone use and longer hospital stay, resulting more severe medical and socio-economic burden and arousing great concern both at home and abroad. This article summarizes the etiological and epidemiological characteristics of M. pneumoniae, commonly used antibiotics, the mechanisms and prevalence of drug resistance and related factors, discusses the strategy of antibiotic use in the treatment of M. pneumoniae infection to provide evidence for the improvements of clinical treatment efficacy, systematic surveillance, multidisciplinary collaboration and antibiotic selection for the purpose of mitigation and control of the drug resistance.