Gonorrhea is a major, global public health problem for which there is no vaccine. The continuing emergence of antibiotic-resistant strains raises concerns that untreatable Neisseria gonorrhoeae may become widespread in the near future. Consequently, there is an urgent need for increased efforts towards the development of new anti-gonococcal therapeutics and vaccines, as well as suitable models for potential pre-clinical vaccine trials. Several current issues regarding gonorrhea are discussed herein, including the global burden of disease, the emergence of antibiotic-resistance, the status of vaccine development and, in particular, a focus on the model systems available to evaluate drug and vaccine candidates. Finally, alternative approaches to evaluate vaccine candidates are presented. Such approaches may provide valuable insights into the protective mechanisms, and correlates of protection, required to prevent gonococcal transmission, local infection and disease sequelae.