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The clustered regularly interspaced short palindromic repeats (CRISPR) system of genome editing represents a major technological advance spanning all areas of genetics and downstream applications. CRISPR’s potential impact on treating human disease encompasses all clinical specialties, including areas important to the plastic surgeon such as oncology, wound healing, immunology, and craniofacial malformations. Plastic surgeons should gain familiarity with this gene editing technology, and become active contributors and leaders in applying CRISPR to their respective areas of expertise. This review describes the history and basic mechanism of CRISPR genome editing, highlights current and future applications, and discusses limitations. The authors will consider CRISPR’s potential impact and use in plastic and reconstructive surgery.