Mycoplasma genitalium is associated with acute and chronic urethritis in men. Existing data on infection in women are limited and inconsistent but suggest that M. genitalium is associated with urethritis, cervicitis, pelvic inflammatory disease, and possibly female infertility. Data are inconclusive regarding the role of M. genitalium in adverse pregnancy outcomes and ectopic pregnancy. Available data suggest that azithromycin is superior to doxycycline in treating M. genitalium infection. However, azithromycin-resistant infections have been reported in 3 continents, and the proportion of azithromycin-resistant M. genitalium infection is unknown. Moxifloxacin is the only drug that currently seems to uniformly eradicate M. genitalium. Detection of M. genitalium is hampered by the absence of a commercially available diagnostic test. Persons with persistent pelvic inflammatory disease or clinically significant persistent urethritis or cervicitis should be tested for M. genitalium, if possible. Infected persons who have not previously received azithromycin should receive that drug. Persons in whom azithromycin therapy fails should be treated with moxifloxicin.