DNA interstrand crosslinks (ICLs), which arise when chemical bonds are formed between the two DNA strands, can block DNA replication and transcription when left unrepaired, leading to cell death. These toxic effects have long been exploited in the clinic by treating patients with cancer with ICL-inducing agents. Moreover, these effects are evident in patients with Fanconi anaemia, whose inability to repair ICLs leads to devastating consequences, including developmental defects and cancer predisposition. Years of studying this disease have unravelled the Fanconi anaemia pathway, through which healthy cells sense, process and ultimately repair ICLs.