CRISPR–cas systems provide microbial immunity to invasive genetic elements in many bacteria and most investigated archea. This chapter highlights important advances following the discovery of CRISPR–cas, its function in immunity and the biochemical characterisation of a subset of immune-effector components, which together target and cleave foreign genomes in a sequence-specific manner. These advances encouraged transplantation of engineered CRISPRS–cas components into human cells to induce sequence-targeted double-strand breaks followed by cell-mediated repair, thereby effectively repurposing CRISPR effectors into efficient genome-editing tools exploiting the different eukaryotic repair pathways. The challenges of genome-wide specific targeting versus potentially harmful off-target activity and efforts to improve target specificity using protein engineering are discussed. The chapter concludes with a brief summary of current ongoing human trials involving CRISPR–cas and the challenges facing clinical development of the technology