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Munir Patel, John C Lantis II Department of Vascular Surgery, Mount Sinai St. Luke’s-West Hospital Center, New York, NY, USA Abstract: The role of cellular and tissue-based therapies (CTPs) in the treatment of chronic wounds continues to grow. However, the utility of these is only partially investigated and very few head-to-head studies exist. In general, the ideal CTP would provide a structural matrix which would allow for dermal and epidermal regeneration with a single application. At present, this Holy Grail is very far from where we are. However, new CTPs continue to be designed with the goal of wound closure in mind. Acellular fish skin (AFS) is one such therapy. The histologic features make it amenable to cellular modulation, and its ability to provide omega-3 fatty acids to the local tissue makes it an unprecedented anti-inflammatory, antibacterial, antiviral, and analgesic component. There is burgeoning research on AFS that continues to validate its efficacy, although, much more substantial data will be required before its general acceptance. In this review, we will go through the current literature to evaluate the strengths and gaps in our current knowledge with the goal of providing a context for use in modern clinical practice. Keywords: fish skin, chronic wounds, dermal matrix