Mycoplasma genitalium was first isolated in 1980 from two of 13 men with non-gonococcal urethritis (NGU). It shares several features with M. pneumoniae, a recognized respiratory tract pathogen. It is extremely difficult to isolate by culture. The development of sensitive and specific polymerase chain reaction (PCR) assays in the early 1990s made clinical studies possible and a significant number of publications have shown a strong association between M. genitalium and NGU, independent of Chlamydia trachomatis. The purpose of this review is to evaluate the currently available information on the associations between M. genitalium and urogenital tract infections in men and women and assess their fulfilment of the Henle–Koch postulates. It is concluded that there is very strong evidence that M. genitalium is a cause of NGU in men and cervicitis in women. Evidence for upper genital tract infections in women has begun to accrue, but further studies are needed. The optimal treatment of M. genitalium infections remains to be determined, but antibiotics of the macrolide group appear to be more active than tetracyclines.