In the United States, gonorrhea is the second most commonly reported notifiable disease, with 339,593 cases documented in 2005. Since 1993, fluoroquinolones (i.e., ciprofloxacin, ofloxacin, or levofloxacin) have been used frequently in the treatment of gonorrhea because of their high efficacy, ready availability, and convenience as a single-dose, oral therapy. However, prevalence of fluoroquinolone resistance in Neisseria gonorrhoeae has been increasing and is becoming widespread in the United States, necessitating changes in treatment regimens. Beginning in 2000, fluoroquinolones were no longer recommended for gonorrhea treatment in persons who acquired their infections in Asia or the Pacific Islands (including Hawaii); in 2002, this recommendation was extended to California. In 2004, CDC recommended that fluoroquinolones not be used in the United States to treat gonorrhea in men who have sex with men (MSM). This report, based on data from the Gonococcal Isolate Surveillance Project (GISP), summarizes data on fluoroquinolone-resistant N. gonorrhoeae (QRNG) in heterosexual males and in MSM throughout the United States. This report also updates CDC's Sexually Transmitted Diseases Treatment Guidelines, 2006 regarding the treatment of infections caused by N. gonorrhoeae. On the basis of the most recent evidence, CDC no longer recommends the use of fluoroquinolones for the treatment of gonococcal infections and associated conditions such as pelvic inflammatory disease (PID). Consequently, only one class of drugs, the cephalosporins, is still recommended and available for the treatment of gonorrhea.