CRISPR-Cas9, a revolutionary gene-editing tool, is emerging as a game-changing solution to the global health crisis of antibiotic resistance. This technology works by precisely identifying and disabling resistance genes within bacterial genomes, effectively neutralizing the mechanisms that render bacteria resistant to antibiotics. Unlike traditional antibiotics, which often indiscriminately kill both harmful and beneficial microbes, CRISPR’s precision ensures that only targeted resistance genes are affected, preserving the balance of beneficial microbiomes. This targeted approach not only minimizes collateral damage but also reduces the selective pressure that drives the emergence of new resistant strains. Furthermore, CRISPR’s adaptability allows it to be customized to target a wide range of resistance genes across various bacterial species, making it a versatile tool in combating this evolving threat. Applications of CRISPR in this field are diverse, from developing therapies that deliver gene-editing systems directly to infection sites, to engineering probiotics that deactivate resistance genes, and even addressing environmental reservoirs of resistance genes in wastewater and soil. While challenges like delivery mechanisms, ethical considerations, and regulatory oversight remain, CRISPR offers an unprecedented opportunity to restore the efficacy of antibiotics and transform the fight against superbugs, safeguarding the future of global healthcare.