Progressively decreasing susceptibility of Neisseria gonorrhoeae to the antibiotics recommended for treatment has raised concerns about the public health threat of antibiotic resistant gonorrhea. This is not a new process, and the organism has reliably developed resistance to all modern antibiotics used for treatment since the dawn of the antibiotic era. The history of changing recommendations for gonorrhea therapy is complex, however, and has been influenced by diagnostic test methods and surveillance. Understanding the impact of these influences may provide insights into current approaches to address this reemerging public health challenge. We reviewed available methods for gonorrhea diagnosis, and public health recommendations for gonorrhea treatment. The literature review was supplemented by qualitative interviews with senior investigators whose research helped shape gonorrhea management strategies over the past 50 years. The process of development of antimicrobial resistance to the antibiotics widely used for treatment seems to be inexorable. Many currently voiced concerns are similar to those raised in the past. The public health threat of increasing antimicrobial resistance by N. gonorrhoeae has been amplified as a result of a smaller pipeline introducing new drugs for gonorrhea treatment. Improved methods for gonorrhea diagnosis have also repeatedly influenced appreciation of the burden of disease caused by N. gonorrhoeae. US Public Health Service leadership has also shaped and improved the management of this important public health problem.