Topoisomerase enzymes – found in prokaryotes to human cells – control conformational changes in DNA and aid the orderly progression of DNA replication, gene transcription and the separation of daughter chromosomes at cell division. Several classes of anti‐cancer drugs are now recognised as topoisomerase poisons because of their ability to trap topoisomerase molecules on DNA as ‘cleavable complexes’. Understanding how drugs generate such complexes and why they are toxic to actively growing cancer cells is a major challenge for the development (...) of modern approaches to chemotherapy. (shrink)