Population growth, famines, climate change, and other issues are just some of the barriers that agriculture needs to overcome to provide food to meet world population needs while maintaining food safety and nutritional value. The wheat (Triticum aestivum) is enormously important for human nutrition, as a source of carbohydrates (and thus calories), fiber, protein, vitamins, and micronutrients. It is the second most-produced crop after maize (Zea mays) with 808 million tons of grain produced in 2021–2022. Plant breeding has played an important role in meeting the ever-growing demand for agricultural produce and will do so for decades to come. This will be aided by new technologies, and here we discuss how clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) nucleases technology can be harnessed for the improvement of agricultural genetics and wheat. The emerging applications and implications of the CRISPR-Cas system have raised new regulatory issues globally, from moral, ethical, social, safety, and technology points of view regarding its applications in preclinical and clinical research, biomedicine, and agriculture. Most importantly, this chapter also concentrates on the ethical and societal issues and further challenges related to the use of the CRISPR-Cas system in plant genome editing.