In bacteria, metal ion resistance requires the contribution of multiple layers of mechanisms such as transport, sequestration, precipitation, or enzymatic transformation. The Gram‐negative bacterium
Cupriavidus metallidurans
CH34 displays an extraordinary metal ion resistance phenotype and can thrive in the presence of millimolar concentrations of toxic metal ions. Resistance of this bacterium to metal ions predominantly relies on the efflux of these noxious compounds out of the cell regulated by membrane transporters. Notably, the genes encoding 12 proteins belonging to the resistance‐nodulation‐cell division (RND) superfamily, and predicted to be involved in metal ion resistance, were detected in the genome of strain CH34. These antiporters form transenvelope protein complexes in combination with proteins belonging to the outer membrane factor (OMF) and the membrane fusion protein (MFP) families. In interplay with other transporters from the cation diffusion facilitator (CDF) and the P‐type ATPase families that detoxify the cytoplasm, the tripartite RND‐driven systems most probably export the toxic metal cations from the periplasm to the outside of the cell. The functional and structural data of proteins constituting one of these 12 predicted tripartite efflux systems, ZneBAC, are reviewed.