Despite nearly a century of therapy for gonococcal infection with a variety of antimicrobials, more than 80 million cases of the disease are reported annually worldwide. The gonorrhea pathogen, Neisseria gonorrhoeae, exhibits an exceptional capability of developing antimicrobial resistance due to its high genetic flexibility. As an obligate pathogen, the gonococcus has evolved mechanisms to evade host defenses by engaging with the innate and adaptive immune responses in both men and women. N. gonorrhoeae can establish residence within epithelial cells, macrophages, and neutrophils. Strains resistant to each of the drugs used in gonorrhea therapy have emerged via genetic variation and horizontal gene transfer. The type IV secretion system plays a critical role in horizontal gene transfer (HGT), driving the evolvement of antimicrobial resistance. The review explores the pathogenesis and immune evasion mechanisms, antimicrobial resistance, genetic variability, laboratory analysis methods for the pathogen, and emerging trends in diagnosis and treatment of gonococcal infections.