Recent developments in clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein (CRISPR/Cas) enable scientists to add critical agronomic traits in crop plants such as plant disease management and tolerance to abiotic stresses. CRISPR-based editing technology not only improved the genetic studies but also shortened out various breeding technologies in an environmentally friendly manner. CRISPR/Cas has overhauled additional genome editing technologies (GETs), for instance, transcription activator-like effector nucleases (TALENs), zinc finger nucleases (ZFNs) and mega-nucleases, because of its simplicity, higher success, robustness and being economical. However, although CRISPR/Cas has emerged as a potent tool in crop genome editing, it is still challenging for scientists to overcome some challenges associated with it, such as off-site targeting and various regulations. Moreover, according to an estimate of the International Society for Plant Pathology, globally, every year there is a reduction of ~10–40% in yield of major cereal crops (Triticum, Oryza, Zea mays, Glycine max), vegetables crops (potato, tomato, egg fruit, beans) and fruit crops (apple, cassava, citrus, grape, avocado) due to various pathogens. Therefore, after years of decryption of CRISPR/Cas technology, researchers are now editing the genomes of crops to solve future food security by generating pathogen-resistant plants. This chapter mainly summarizes an updated utilization of CRISPR/Cas and/or CRISPR-associated proteins in cultivated and model crop disease management in response to various pathogens.