The incidence of Neisseria gonorrhoeae infections in the United States has grown over the past decade. The most recent data provided by the Centers for Disease Control and Prevention (CDC) indicate that reported cases have increased by almost 10% over the last 5 years. In conjunction with this rise, the presence of multidrug-resistant strains of N. gonorrhoeae has also emerged. The 2015 CDC guidelines recommend dual therapy with intramuscular ceftriaxone and oral azithromycin as first-line treatment, although components of this regimen are met with a high level of resistance. Although ceftriaxone resistance has not yet been reported in the United States, it is only a matter of time before such isolates are detected, thus ushering in a new era of difficult-to-manage uncomplicated gonococcal infection. The potential public health crisis and patient-associated sequelae (e.g., pelvic inflammatory disease, epididymitis, and human immunodeficiency virus infection) linked with untreatable gonorrhea are cause for great concern. To try to stem this tide, a number of new agents targeted against N. gonorrhoeae are being investigated in clinical trials. In this article, we review the various agents, both currently available and under clinical investigation, and provide recommendations for the management of gonococcal infections.