Prevention and control of gonorrhea is an important public health concern due to the high burden of disease, the recent increase in reported infection rates, and the reproductive and economic consequences of infection. Effective antibiotic treatment is one essential component of an integrated approach to gonorrhea control. Over the past 60 years, however, development of resistance in Neisseria gonorrhoeae to multiple antimicrobial classes challenges this component of gonorrhea control. An integrated, comprehensive prevention strategy should include enhancement of national and international surveillance systems to monitor antimicrobial resistance and new strategies to maximize the benefit and prolong the utility of antimicrobials, including combination regimens, implementation of screening recommendations for individuals at high risk for infection, and the assurance of prompt and effective treatment for infected persons and their sexual partners. Progress in controlling the epidemic and avoiding a resurgence as treatment options wane will require careful attention to all components of a comprehensive prevention strategy.