Vast swathes of hematology and immunology have been illuminated with gene-targeting approaches. The past two decades have witnessed the development of several generations of engineered nucleases that offer great opportunity for gene therapy. The field changed dramatically with the advent of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) as a tool to edit the genome of human cells. CRISPR/Cas9 the cheapest, most efficient, and easiest to scale up genome editing technology to date. Since the first demonstration of the feasibility of editing genes in primary human hematopoietic stem cells (HSCs) and T cells using CRISPR/Cas9 in 2014 (Mandal & Ferreira et al., 2014; Meissner et al., 2014), tremendous progress has been made in our capacity to perform CRISPR-mediated gene modifications in human blood cells.