Mycoplasma genitalium was first isolated from men with non-gonococcal urethritis (NGU) more than 20 years ago. Use of polymerase chain reaction technology has shown it to be a cause of acute NGU and probably chronic NGU, almost independently of Chlamydia trachomatis, but there is no substantial evidence that it causes acute or chronic prostatitis. In women, M. genitalium is not associated with bacterial vaginosis, but it is strongly associated with cervicitis and endometritis and serologically with salpingitis and tubal factor infertility. Further studies may show M. genitalium to be associated, perhaps causally, with epididymoorchitis, neonatal disease and reactive arthritis. Furthermore, its potential for enhancing HIV transmission needs to be explored. M. genitalium is susceptible to various broad-spectrum antibiotics, but M. genitalium-associated diseases are probably best treated with azithromycin.