The term MDR (Multi Drug Resistance) system refers to a group of transporters which are able to expulse a wide range of quite different substrates. While this type of system was first described in eukaryotic cells in the late 1980s, the presence of MDR efflux-pumps in bacteria showing resistance to several drugs has been increasingly reported in the literature. Under laboratory conditions the expression of these MDR systems is usually down-regulated. On occasion, basal expression of these efflux pumps is allowed in wild type strains, thus suggesting a role of these MDR systems in the intrinsic of these microorganisms resistance to antibiotics. On the other hand, overexpression of these MDR efflux pumps, after induction or because of the emergence of mutations in their regulatory elements, is also important in acquired resistance to antibiotics. This review summarizes the most relevant features of the MDR systems described in bacteria, as well as the mechanisms that regulate their expression.