Efflux pumps can make a significant contribution to the capacity of bacteria to resist the action of antibiotics. Certain efflux pumps also recognize antimicrobial agents that are present in their respective hosts and their ability to export toxic agents could enhance bacterial survival during infection prior to appearance of cellular or humoral host defensive systems. This review is concerned with the principal efflux pumps possessed by two closely related strict human pathogens, Neisseria gonorrhoeae and Neisseria meningitidis. Specific emphasis is placed on the organization of the structural genes encoding the mtr and far efflux pumps, the substrates (often host-derived) recognized by these pumps, and the cis- and trans-acting transcriptional factors that regulate efflux pump gene expression in gonococci and meningococci. The overriding theme of this review is that the efflux pumps possessed by these pathogens likely contribute to their pathogenic mechanisms by providing a means to escape a number of antimicrobial compounds that bathe mucosal surfaces.