Mycoplasma genitalium is a globally important sexually transmitted pathogen. Men infected with M. genitalium frequently present with dysuria, while women may present with or without urogenital symptoms. In some populations, M. genitalium is significantly associated with HIV-1 infection, and is also an etiological agent in pelvic inflammatory disease. However, there is insufficient evidence to establish a causative role of the organism in obstetric complications, including tubal factor infertility. Although several nucleic acid amplification tests offer rapid, sensitive methods for detecting M. genitalium, there is no standardized assay. Available evidence supports treatment of M. genitalium infections with an extended regimen of azithromycin and resistant strains respond to moxifloxacin. Accumulating evidence indicates growing fluoroquinolone resistance, including against moxifloxacin, emphasizing the need for new therapeutic strategies to treat M. genitalium infections.