Mycoplasma pneumoniae is one of major pathogens causing respiratory tract infection of children and is usually treated with macrolides. Since 2001, reported macrolide resistant isolates of Mycoplasma pneumoniae has increased worldwide, especially in East Asia. This paper reviews the current situation and mechanisms of macrolide resistance of Mycoplasma pneumoniae and clinical characteristics of pediatric patients infected by macrolide resistant Mycoplasma pneumoniae, and discusses the best approach to deal with this situation.