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Mycoplasma pneumoniae is a common cause of respiratory tract infections (RTI's), especially in children. While severe M. pneumoniae infections are generally treated with antibiotics, the diagnosis as well as treatment of these infections should be reconsidered in the light of recent clinical findings. First, M. pneumoniae was found to be carried in the upper respiratory tract of a relatively high percentage of healthy, asymptomatic children. Clearly, this complicates the diagnosis of a suspected M. pneumoniae RTI and, thus, the decision when to initiate treatment. A complication in the treatment of these infections is that data on the efficacy of antibiotic treatment of M. pneumoniae RTI's are sparse and derived exclusively from comparative studies. A recent Cochrane review concluded that there is insufficient evidence about the efficacy of antibiotics for M. pneumoniae lower respiratory tract infections (LRTI) in children. Due to side effects associated with the use of tetracyclines and quinolones in children, only macrolides can be used to treat M. pneumoniae infections in young patients. The general applicability of macrolides, however, is currently threatened by the worldwide increase in macrolide-resistant M. pneumoniae strains. Finally, limited evidence is available that corticosteroids might have an additional benefit in the treatment of M. pneumoniae infections. In this review, the current issues related to the diagnosis and treatment of M. pneumoniae infections will be discussed.