The history of gonococcal resistance to antibiotics will be reviewed with a focus on the contribution of efflux pumps in permitting gonococci to avoid killing by their action. The structure, function and regulation of a major multidrug efflux pump (MtrCDE) will be highlighted with respect to bacterial resistance to beta-lactam and macrolide antibiotics as well as a new DNA gyrase inhibitor that will likely have increased clinical use in the future. Finally, considerations of future areas of research will be presented.