CRISPR–Cas technologies have revolutionized genome editing, enabling precise manipulation of DNA and RNA in diverse species. The ease and robustness of these systems have transformed research across fundamental science to translational medicine. New CRISPR–Cas systems, including Cas9, Cas12a, Cascade, and Cas13, have expanded targeting capabilities and applications. These systems utilize non-homologous end joining (NHEJ) and homology-directed repair (HDR) for DNA repair, as well as single-base editing enzymes. CRISPR–Cas-based RNA-targeting tools are being developed for research, medicine, and diagnostics. Nuclease-inactive and RNA-targeting Cas proteins have been fused to various effector proteins to regulate gene expression, epigenetic modifications, and chromatin interactions. These advances are enhancing our understanding of biology and advancing CRISPR–Cas-based tools toward clinical use in gene and cell therapies. CRISPR–Cas9 is a class 2 type II system that generates double-strand breaks (DSBs) at specific sites. It recognizes a PAM sequence (5'-NGG) and is widely used for genome editing. Variants of Cas9 with altered PAM specificities have been developed to increase target availability. Cas12a, a type V system, generates staggered cuts and can cleave crRNA arrays, enabling simplified multiplexed genome editing. Cascade and Cas3 are type I systems that offer greater target site flexibility and are being used for antimicrobial applications. Cas13, a type III system, targets RNA and has been used for RNA detection and editing. These systems have expanded the CRISPR toolbox for genome editing. CRISPR–Cas systems are used for gene editing, including gene deletions, insertions, and translocations. HDR is used for precise genomic alterations, while NHEJ is used for gene knockouts. Single-base editing tools, such as BE3 and BE4, enable precise nucleotide changes. High-throughput loss-of-function screens using CRISPR–Cas9 have been used to identify gene functions and therapeutic targets. These screens have been applied to study non-coding genomes and identify regulatory elements. CRISPR–Cas systems are also used for gene regulation, including transcriptional repression (CRISPRi) and activation (CRISPRa), as well as epigenome editing. These systems are being used to study chromatin interactions and gene expression. CRISPR–Cas systems are being used for imaging loci and tracking cellular responses. These systems have been used to develop molecular recording tools that track cellular behavior in response to stimuli. CRISPR–Cas systems are also being used for RNA targeting, including RCas9 and Cas9 orthologs that can target RNA. These systems have been used for RNA detection, editing, and therapeutic applications. Overall, CRISPR–Cas technologies are advancing our understanding of biology and enablingCRISPR–Cas technologies have revolutionized genome editing, enabling precise manipulation of DNA and RNA in diverse species. The ease and robustness of these systems have transformed research across fundamental science to translational medicine. New CRISPR–Cas systems, including Cas9, Cas12a, Cascade, and Cas13, have expanded targeting capabilities and applications. These systems utilize non-homologous end joining (NHEJ) and homology-directed repair (HDR) for DNA repair, as well as single-base editing enzymes. CRISPR–Cas-based RNA-targeting tools are being developed for research, medicine, and diagnostics. Nuclease-inactive and RNA-targeting Cas proteins have been fused to various effector proteins to regulate gene expression, epigenetic modifications, and chromatin interactions. These advances are enhancing our understanding of biology and advancing CRISPR–Cas-based tools toward clinical use in gene and cell therapies. CRISPR–Cas9 is a class 2 type II system that generates double-strand breaks (DSBs) at specific sites. It recognizes a PAM sequence (5'-NGG) and is widely used for genome editing. Variants of Cas9 with altered PAM specificities have been developed to increase target availability. Cas12a, a type V system, generates staggered cuts and can cleave crRNA arrays, enabling simplified multiplexed genome editing. Cascade and Cas3 are type I systems that offer greater target site flexibility and are being used for antimicrobial applications. Cas13, a type III system, targets RNA and has been used for RNA detection and editing. These systems have expanded the CRISPR toolbox for genome editing. CRISPR–Cas systems are used for gene editing, including gene deletions, insertions, and translocations. HDR is used for precise genomic alterations, while NHEJ is used for gene knockouts. Single-base editing tools, such as BE3 and BE4, enable precise nucleotide changes. High-throughput loss-of-function screens using CRISPR–Cas9 have been used to identify gene functions and therapeutic targets. These screens have been applied to study non-coding genomes and identify regulatory elements. CRISPR–Cas systems are also used for gene regulation, including transcriptional repression (CRISPRi) and activation (CRISPRa), as well as epigenome editing. These systems are being used to study chromatin interactions and gene expression. CRISPR–Cas systems are being used for imaging loci and tracking cellular responses. These systems have been used to develop molecular recording tools that track cellular behavior in response to stimuli. CRISPR–Cas systems are also being used for RNA targeting, including RCas9 and Cas9 orthologs that can target RNA. These systems have been used for RNA detection, editing, and therapeutic applications. Overall, CRISPR–Cas technologies are advancing our understanding of biology and enabling