The efflux systems of bacteria protect cells from antibiotics and biocides by 
actively transporting compounds out of the cytoplasm and/or periplasm and 
thereby limit their steady-state accumulation at their site(s) of action. The 
impact of efflux systems on the efficacy of antibiotics used in human medicine 
and animal husbandry is becoming increasingly apparent from the characterization 
of drug-resistant strains with altered drug efflux properties. In most 
instances, efflux-mediated antibiotic resistance arises from mutational events 
that result in their elevated expression and, in the case of efflux pumps with 
broad substrate specificity, can confer multi-drug resistance (MDR) to 
structurally unrelated antibiotics. Knowledge of the role of efflux systems in 
conferring antibiotic resistance has now been successfully exploited in the 
pharmaceutical industry and contributed, in part, to the development of new 
members of the macrolide and tetracycline classes of antibiotics that circumvent 
the efflux-based resistance mechanisms that have limited the clinical utility of 
their progenitors. The therapeutic utility of compounds that inhibit bacterial 
drug efflux pumps and therein potentiate the activity of a co-administered 
antibiotic agent remains to be validated in the clinical setting, but the 
approach holds promise for the future in improving the efficacy and/or extending 
the clinical utility of existing antibiotics. This review discusses the 
potential of further exploiting the knowledge of efflux-mediated antibiotic 
resistance in bacteria toward the discovery and development of new 
chemotherapeutic agents.