In modern practice, xenografts play a crucial role in wound management due to their regenerative properties. Of the various xenografts currently available on the market, acellular fish skin (AFS) grafts have emerged as a more effective alternative to existing xenografts and other standard of care (SOC) treatments for wound healing. Since AFS grafts require minimal processing, they maintain their structural integrity and natural properties, including an abundance of Omega-3 fatty acids, which is a distinctive, pro-regenerative feature. AFS grafts are also unique in that they are not derived from mammalian tissue, so there is no risk of viral transmission and no cultural or religious barriers to use. AFS grafts have been shown to be more cost-effective in the treatment of diabetic foot ulcers (DFUs) and result in a higher percentage of healed wounds, fewer amputations, and better patient quality of life. Several studies and case reports have highlighted the versatility of AFS in not only acute and chronic wound healing, but also for burn wound skin regeneration. Additionally, AFS may have promise as an implantable biologic matrix for suture line reinforcement in hernia repairs or breast and dura reconstruction.