Application of the recently developed CRISPR/Cas tools might help enhance cereals' growth and yield under biotic and abiotic stresses. Cereals are the most important food crops for human life and an essential source of nutrients for people in developed and developing countries. The growth and yield of all major cereals are affected by both biotic and abiotic stresses. To date, molecular breeding and functional genomic studies have contributed to the understanding and improving cereals' growth and yield under biotic and abiotic stresses. Clustered, regularly inter-spaced, short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) system has been predicted to play a major role in precision plant breeding and developing non-transgenic cereals that can tolerate adverse effects of climate change. Variants of next-generation CRISPR/Cas tools, such as prime editor, base editor, CRISPR activator and repressor, chromatin imager, Cas12a, and Cas12b, are currently used in various fields, including plant science. However, few studies have been reported on applying the CRISPR/Cas system to understand the mechanism of biotic and abiotic stress tolerance in cereals. Rice is the only plant used frequently for such studies. Genes responsible for biotic and abiotic stress tolerance have not yet been studied by CRISPR/Cas system in other major cereals (sorghum, barley, maize and small millets). Examining the role of genes that respond to biotic and abiotic stresses using the CRISPR/Cas system may help enhance cereals' growth and yield under biotic and abiotic stresses. It will help to develop new and improved cultivars with biotic- and abiotic-tolerant traits for better yields to strengthen food security. This review provides information for cereal researchers on the current status of the CRISPR/Cas system for improving biotic and abiotic stress tolerance in cereals.