Epidermolysis bullosa (EB) is a rare, monogenetic skin disease characterized by blister formation upon minimal mechanical stress. It is caused by mutations in genes encoding proteins essential for skin structure. Current treatments are limited to wound management, but gene therapy offers a potential cure. Two promising gene therapies are under development: gene replacement and gene editing. Beremagene geperpavec (B-VEC), a gene replacement therapy, was approved by the FDA for severe EB, marking a significant breakthrough. Gene editing, including CRISPR/Cas9, is also being explored for precise mutation repair. Ex vivo gene replacement therapies have shown success in clinical trials, with long-term benefits observed in patients. In vivo gene replacement, such as B-VEC, is now available for topical treatment of RDEB. Gene editing, while still preclinical, holds promise for future EB treatment. CRISPR/Cas9 has shown high efficiency and specificity, with modifications improving its precision. However, challenges remain in delivery and long-term safety. Ongoing trials aim to evaluate the efficacy and safety of these therapies, with the goal of providing effective, long-term treatments for EB patients.Epidermolysis bullosa (EB) is a rare, monogenetic skin disease characterized by blister formation upon minimal mechanical stress. It is caused by mutations in genes encoding proteins essential for skin structure. Current treatments are limited to wound management, but gene therapy offers a potential cure. Two promising gene therapies are under development: gene replacement and gene editing. Beremagene geperpavec (B-VEC), a gene replacement therapy, was approved by the FDA for severe EB, marking a significant breakthrough. Gene editing, including CRISPR/Cas9, is also being explored for precise mutation repair. Ex vivo gene replacement therapies have shown success in clinical trials, with long-term benefits observed in patients. In vivo gene replacement, such as B-VEC, is now available for topical treatment of RDEB. Gene editing, while still preclinical, holds promise for future EB treatment. CRISPR/Cas9 has shown high efficiency and specificity, with modifications improving its precision. However, challenges remain in delivery and long-term safety. Ongoing trials aim to evaluate the efficacy and safety of these therapies, with the goal of providing effective, long-term treatments for EB patients.