Mycoplasma is a well-recognised pathogen that colonises mucosal surfaces of humans and animals. Mycoplasma pneumoniae infects the upper and lower respiratory tracts of children and adults, leading to a wide range of respiratory and non-respiratory clinical conditions. M. pneumoniae infection is frequently considered in the differential diagnosis of patients with respiratory illnesses, and is commonly managed empirically with macrolides and fluoroquinolones. This contrasts with patients who present with non-respiratory symptoms in the context of a recent or current unrecognised M. pneumoniae infection, for whom this pathogen is rarely considered in the initial differential diagnosis. This review considers the microbiological, epidemiological, pathogenic and clinical features of this frequent pathogen that need to be considered in the differential diagnosis of respiratory and non-respiratory infections.