M. pneumoniae infection gives rise to a wide variety of manifestations. The pathogenesis of secondary manifestations is not always known. Some depend on the direct invasion of M. pneumoniae and others on the indirect effect of M. pneumoniae through pathological immune responses, for instance autoreactive antibodies in Guillain-Barré Syndrome. Diagnosis remains challenging with currently available diagnostic tests, because they do not demonstrate a causal relation due to M. pneumoniae asymptomatic carriage or previous infection. The mainstay of treatment is macrolide antibiotics, but the role of additional immunomodulation therapy is unclear. Knowledge of the pathogenesis of the different manifestations should guide strategies for diagnosis and treatment.