The article reviews the mechanisms underlying off-target effects in the CRISPR/Cas9 genome-editing system, methods for detecting these effects, and strategies to minimize them. Off-target mutations, which occur at frequencies greater than 50%, pose significant concerns for therapeutic and clinical applications. The mechanisms of off-target cutting involve the seed sequence and the PAM (protospacer adjacent motif) sequence in the sgRNA. The seed sequence, particularly the 10-12 base pairs adjacent to the PAM, is crucial for Cas9 specificity. Off-target detection methods, such as deep sequencing, web-based prediction tools, and ChIP-seq, have been developed to identify these mutations. Strategies to minimize off-target effects include altering sgRNA sequences, controlling the concentration of the Cas9-sgRNA complex, using double nicking, and fusing catalytically inactive Cas9 with FokI nuclease. The article also discusses the potential of new CRISPR/Cas9 variants and other gene-editing technologies, highlighting the ongoing efforts to improve the specificity and efficiency of genome editing.The article reviews the mechanisms underlying off-target effects in the CRISPR/Cas9 genome-editing system, methods for detecting these effects, and strategies to minimize them. Off-target mutations, which occur at frequencies greater than 50%, pose significant concerns for therapeutic and clinical applications. The mechanisms of off-target cutting involve the seed sequence and the PAM (protospacer adjacent motif) sequence in the sgRNA. The seed sequence, particularly the 10-12 base pairs adjacent to the PAM, is crucial for Cas9 specificity. Off-target detection methods, such as deep sequencing, web-based prediction tools, and ChIP-seq, have been developed to identify these mutations. Strategies to minimize off-target effects include altering sgRNA sequences, controlling the concentration of the Cas9-sgRNA complex, using double nicking, and fusing catalytically inactive Cas9 with FokI nuclease. The article also discusses the potential of new CRISPR/Cas9 variants and other gene-editing technologies, highlighting the ongoing efforts to improve the specificity and efficiency of genome editing.