Various genome editing tools have been developed for programmable genome manipulation at specified genomic loci. However, it is crucial to comprehensively interrogate the off-target effect induced by these genome editing tools, especially when apply them onto the therapeutic applications. Here, we outlined the off-target effect that has been observed for various genome editing tools. We also reviewed detection methods to determine or evaluate the off-target editing, and we have discussed their advantages and limitations. Additionally, we have summarized current RNA editing tools for RNA therapy and medicine that may serve as alternative approaches for genome editing tools in both research and clinical applications.