This review provides a comprehensive overview of the current state and future potential of CRISPR genome editing technologies. It begins by tracing the historical development of genome editing, from early studies using homing endonucleases to the advent of engineered nuclease enzymes like ZFNs and TALENs, and ultimately to the revolutionary discovery of RNA-guided CRISPR-Cas systems. The review highlights the transformative impact of CRISPR-based technologies on various fields, including molecular biology, medicine, agriculture, and biotechnology. The review discusses the limitations of CRISPR genome editing, particularly off-target activity and the need for DSB repair mechanisms, and outlines technological innovations to address these challenges. These include the development of high-fidelity nuclease variants, guide RNA modifications, and alternative PAM-specific Cas9 orthologs. The review also explores the expanded landscape of CRISPR technologies, such as base editing and prime editing, which offer more precise and efficient ways to introduce genetic modifications without generating DSBs. The current applications of CRISPR genome editing in basic research and human medicine are discussed, including the use of CRISPR for disease modeling, therapeutic gene editing, and the development of molecular diagnostics. The review concludes by outlining potential future developments, emphasizing the ongoing efforts to improve the specificity, efficiency, and safety of CRISPR-based technologies.This review provides a comprehensive overview of the current state and future potential of CRISPR genome editing technologies. It begins by tracing the historical development of genome editing, from early studies using homing endonucleases to the advent of engineered nuclease enzymes like ZFNs and TALENs, and ultimately to the revolutionary discovery of RNA-guided CRISPR-Cas systems. The review highlights the transformative impact of CRISPR-based technologies on various fields, including molecular biology, medicine, agriculture, and biotechnology. The review discusses the limitations of CRISPR genome editing, particularly off-target activity and the need for DSB repair mechanisms, and outlines technological innovations to address these challenges. These include the development of high-fidelity nuclease variants, guide RNA modifications, and alternative PAM-specific Cas9 orthologs. The review also explores the expanded landscape of CRISPR technologies, such as base editing and prime editing, which offer more precise and efficient ways to introduce genetic modifications without generating DSBs. The current applications of CRISPR genome editing in basic research and human medicine are discussed, including the use of CRISPR for disease modeling, therapeutic gene editing, and the development of molecular diagnostics. The review concludes by outlining potential future developments, emphasizing the ongoing efforts to improve the specificity, efficiency, and safety of CRISPR-based technologies.