While driver mutations in cancer genomes were the main focus of cancer research for a long time, passenger mutational signatures - the imprints of DNA damage and DNA repair processes that have been operative during tumorigenesis - are also biologically informative. In this lecture, I provide an update of where we are in untangling the mechanisms underpinning mutation patterns in human somatic cells, describing the new insights that we have gained through combinations of computational analysis and experiments in cell-based systems, and showcase how we have developed the concept into applications that we hope to translate into clinical utility in the near future.