© David Schlossberg 2008. Mycoplasmas are the smallest free-living organisms and are unique among prokaryotes in that they lack a cell wall, a feature that is largely responsible for their biologic properties and lack of susceptibility to many commonly prescribed antimicrobial agents. Mycoplasmas are usually mucosally associated, residing primarily in the respiratory and urogenital tracts and rarely penetrating the submucosa, except in the case of immunosuppression or instrumentation, when they may invade the bloodstream and disseminate to many different organs and tissues throughout the body. Intracellular localization occurs in some species and may contribute to chronicity that characterizes many mycoplasmal infections. There are at least 17 species of mycoplasmas and ureaplasmas for which humans are believed to be the primary host, and numerous others of animal origin that have been detected occasionally, most often in the setting of immunosuppression. Several human mycoplasmal species are commensals in the upper respiratory or lower urogenital tracts. Five species are responsible for the majority of clinically significant infections that may come to the attention of the practicing physician. These species are Mycoplasma pneumoniae, Mycoplasma hominis, Mycoplasma genitalium, Ureaplasma urealyticum, and Ureaplasma parvum. Mycoplasma fermentans is another mycoplasma of human origin that may behave as an opportunist. Mycoplasma fermentans has been detected in throat cultures of children with pneumonia, in some cases when no other etiologic agent was identified, but the frequency of its occurrence in healthy children is not known. This mycoplasma has also been detected in adults with an acute influenzalike illness and in bronchoalveolar lavage specimens from patients with the acquired immunodeficiency syndrome and pneumonia.