Bacterial pathogens use TolC-dependent machineries to export toxins and enzymes by bypassing the periplasm via a tripartite apparatus in which the outer membrane TolC protein is recruited by a substrate-engaged inner membrane translocase of a traffic ATPase and an accessory or ‘adaptor’ protein. This establishes a contiguous export channel from the cytosol to the outside. Our work has focused on export of the large hemolysin toxin by uropathogenic and enterohemorrhagic E. coli, and I will summarize our view of this process. Closely related TolC-dependent tripartite machines are ubiquitous in the the cell envelopes of bacteria like Escherichia coli and Pseudomonas aeruginosa and these expel antibacterial drugs and other small noxious chemicals, so helping the bacteria survive. These multidrug efflux pumps are important to the growing threat of bacterial resistance to chemotherapy. They function similarly by recruitment of a TolC family protein by energised drug-laden translocases in the inner membrane, though in this case the adaptor is typically coupled to a proton antiporter. We have crystallised and solved the 3D structures of the TolC protein, revealing a trimeric exit duct anchored in the outer membrane and projecting across the periplasm, and also the periplasmic adaptor protein that recruits TolC. These structures reveal how the tripartite pumps assemble to a contiguous trans-envelope pores for virulence protein export and multidrug resistance, and we have now established how the recruitment and pump assembly is effected by interaction of TolC-adaptor coiled-coil interfaces in the periplasm. We have described how the periplasmic exit duct entrance can be opened in the assembled pumps to allow exit of toxins and drugs, and also shown how the entrance constriction can be blocked by potential inhibitors. This suggests it may be possible to develop new drugs to target the pumps and counteract multidrug resistance.