The incidence of gonorrhea is increasing in developed countries and remains high elsewhere. This untenable disease burden, the complication rate in women and newborns, and the amplification of human immunodeficiency virus transmission that accompanies gonorrhea makes control of gonococcal disease a priority. However, antibiotic resistance in Neisseria gonorrhoeae has severely compromised the successful treatment of gonorrhea. Older therapies are ineffective, whereas those that remain efficacious are unaffordable in many high-incidence settings. Penicillins, tetracyclines, and newer macrolides have limited utility, and spectinomycin (and in many parts of the world, quinolones) have been withdrawn because of resistance. Of the usually recommended treatments, only the third-generation cephalosporins, and most notably ceftriaxone, have retained their efficacy, but decreased susceptibility to these antibiotics has also appeared. A sustained decrease in gonococcal disease requires an integrated approach combining improved prevention, better diagnosis, and effective treatment. Without continued commitment and effort, gonorrhea may well become untreatable.