SummaryThe first decade of capture‐based targeted whole exome sequencing (WES) has now passed, while the sequencing modality continues to find more widespread usage in clinical research laboratories and still offers an unprecedented diagnostic assay in terms of throughput, informational content and running costs. Until quite recently, WES has been out of reach for many clinicians and molecular biologists, and it still poses issues or is met with some reluctance with regards to cost versus benefit in terms of effective assay costs, hands‐on laboratory work and data analysis bottlenecks. Although WES is used more than ever, it may also be argued that the usage is peaking and that new implementations, or relevance in its current state, will likely be leveling off during the following decade as the price on whole genome sequencing continues to drop. In this review, we focus on the past decade of targeted whole exome sequencing in malignant hematology. We thematically revisit some of the significant discoveries and niches that use next‐generation sequencing, and we outline what and how WES has contributed to the field – from clonal hematopoiesis of the aging bone marrow to profiling malignancies down to the single cell.