The arrival of both high-throughput and bench-top next-generation sequencing technologies and sequence enrichment methods has revolutionized our approach to dissecting the genetic basis of cancer. These technologies have been almost invariably employed in wholegenome sequencing (WGS) and whole-exome sequencing (WES) studies. Both WGS and WES approaches have been widely applied to interrogate the somatic mutational landscape of sporadic cancers and identify novel germline mutations underlying familial cancer syndromes. The clinical implications of cancer genome sequencing have become increasingly clear, for example in diagnostics. In this editorial, we present these advances in the context of research discovery and discuss both the clinical relevance of cancer genome sequencing and the challenges associated with the adoption of these genomic technologies in a clinical setting. The arrival of both high-throughput and bench-top next-generation sequencing technologies and sequence enrichment methods has revolutionized our approach to dissecting the genetic basis of cancer. These technologies have been almost invariably employed in whole genome sequencing (WGS) and whole-exome sequencing Both WGS and WES approaches have been been applied to interrogate the somatic mutational landscape of sporadic cancers and identify novel germline genes underlying geri-cal cancer syndromes. The clinical implications of cancer genome sequencing have become increasingly clear, for example in diagnostics. In this editorial, we present these advances in the context of research discovery and discuss both the clinical relevance of cancer genome sequencing and the challenges associated with the adoption of the genomic technologies in a clinical setting.