Common wheat • Polyploidy genomes • Multiplexed • Sequence-specific genetic editing Bread wheat (Triticum aestivum L.) is the most important staple crop worldwide. Wheat has a large and allohexaploid genome with more than 107 thousand gene models that expand over 21 chromosomes with 3 replicates. The high complexity of the wheat genome has restricted the success of conventional breeding programs. Wheat genome modification by biotechnological methods has been hindered due to the current methods limitations and safety issues over genetically-modified crops. CRISPR/Cas9 is an emerging biotechnological tool that holds promises for multiplexed, sequence-specific, efficient and rapid manipulation of large genomes such as that of wheat. The CRISPR/Cas9 system introduces sequence-specific double-strand breaks (DSBs) in DNA by synthetic nucleases. The targeted genomic loci are then fixed by DNA repair mechanisms such as non-homologous end-joining (NHEJ) or homology-directed repair (HDR). The system and its improved sub-techniques have achieved significant successes in addressing biosafety and legal concerns over genetically-modified plant production. In this chapter, the history, potentials and the latest results of CRISPR/Cas9-based genetic manipulations in bread wheat is reviewed.