© 2017 Indian Institute of Science. Structural biology provides snapshots of biological function of molecular- and atomic-level structures of macromolecules, and holds great promise in addressing the emerging problems of biomedical science. Since the discovery of penicillin in early twentieth century, mankind has become aware and confronted with the emergence of antibiotic-resistant pathogens. In parallel to the failure of antibiotic therapy against infectious pathogens, there had been continuous reports of cancerous cells not responding to chemotherapy with increase in the duration of therapy. Research on the underlying causes of multidrug resistance in cancerous cells and later on in infectious bacteria revealed the involvement of integral membrane transporters, capable of recognizing a broad range of structurally different molecules as substrates and exporting them from the cell using cellular energy. Structural biologists succeeded in determining the structure of AcrB from Escherichia coli in 2002, the first structure of a multidrug resistance (MDR) transporter, and since then rapid progress has been made in the structural elucidation of these transporters. To date, structures of these transporters in apo- and substrate/inhibitor-bound state have been determined and deposited in the protein databank. This repository is a valuable source for structure-based drug design against MDR pumps. In this review, major findings related to structural biology of MDR transporters belonging to three major superfamilies, viz., ATP-binding cassette superfamily, major facilitator superfamily and resistance nodulation division superfamily are presented. Further, the future role of structural biology in improving our understanding of drug-transporter interactions and in designing novel inhibitors against MDR pump are discussed.