Chlamydia and gonorrhea, which are caused by Chlamydia trachomatis serovars D-K (Ct) and Neisseria gonorrhoeae (Ng), respectively, occur at high incidence world-wide and rank first and second among the most frequently reported notifiable infections to the US Centers for Disease Control (CDC). These pathogens are particularly devastating to female reproductive health compared to other STI pathogens. Unfortunately treatment options for Ng have seriously dwindled due to the recent emergence of resistance to the extended spectrum cephalosporins (ESCs), which were the last remaining class of antibiotics recommended for routine monotherapy of gonorrhea. Information on how Ng/Ct co-infection may differ from infection with either pathogen alone is seriously needed to improve diagnostic capabilities and develop dually active therapies.