Bacteria contain an array of transport proteins in their cytoplasmic membrane. Many of these proteins play an important role in conferring resistance to toxic compounds. The multidrug efflux systems encountered in prokaryotic cells are very similar to those observed in eukaryotic cells. Therefore, a study of the factors which determine the substrate specificity and energy coupling to drug translocation in bacteria has significance for the general field of multidrug resistance. Three issues will be dealt with in this review. First, an overview of the various classes of prokaryotic multidrug transporters will be presented. Second, the current understanding of the regulation of bacterial multidrug resistance will be summarized. Third, the present knowledge of the molecular mechanisms involved in drug transport processes will be discussed.