Nucleic acid amplification tests (NAAT) offer enhanced sensitivity and excellent specificity for many sexually transmitted diseases. For some pathogens for which a practical diagnostic test does not exist, such as human papillomavirus (HPV), NAAT are also useful. Further, most NAAT can be applied to less "invasive" patient specimens, including urine and vaginal fluid. This dramatically increases opportunities to test persons outside of traditional clinic settings. Use of NAAT has resulted in revisions of the proportion of sexually transmitted diseases (STDs) that are asymptomatic, and has increased measured prevalence of some STDs, notably Chlamydia trachomatis. NAAT have helped to clarify the eitiologies of genital ulcer disease and urethritis, and have provided a more complete picture of the natural history of genital herpes and HPV. The ability of polymerase chain reaction to detect HPV may change the management of patients who have abnormal Pap smears. Efforts to bear the relatively high cost of NAAT, such as pooling urine, are under study. NAAT for bacterial STD should be in populations at high risk for asymptomatic STD, especially those who might not access routine STD screening at traditional settings. Working through the cost to health care systems, including the public health arena, and implementation at the laboratory level are challenges to overcome before NAAT become the standard of care in most settings.