Fluoroquinolones and broad-spectrum cephalosporins are the most effective antimicrobial agents for the treatment of gonorrhea. However, clinically significant resistance to fluoroquinolones has emerged in Neisseria gonorrhoeae. Fluoroquinolone-resistant strains account for approximately 10% of all gonococcal strains in Hong Kong and the Republic of the Philippines. As many as 50% of strains from some Far Eastern countries exhibit decreased susceptibility (intermediate resistance) to fluoroquinolones. Strains with intermediate resistance and clinically significant resistance are being isolated sporadically in North America, where resistant strains have been associated with an outbreak and with failure of infections to respond to treatment with doses of ciprofloxacin and ofloxacin recommended by the Centers for Disease Control and Prevention; strains exhibiting decreased susceptibility to these agents are endemic in at least one metropolitan area. Monitoring for fluoroquinolone resistance is now critical for ensuring adequate treatment of infections with resistant strains and for maximizing the time during which fluoroquinolones may be used to treat gonorrhea.