Hypertrophic scar and keloid are common and difficult to treat diseases in plastic surgery. Results of wound healing research over the past decades have demonstrated that transforming growth factor-beta (TGF-beta) plays an essential role in cutaneous scar formation. In contrast, fetal wounds, which heal without scarring, contain a lower level of TGF-beta than adult wounds. How to translate the discovery of basic scientific research into the clinical treatment of wound scarring has become an important issue to both clinicians and basic researchers. The development of gene therapy techniques offers the potential to genetically modify adult wound healing to a healing process similar to fetal wounds, and thus reduces wound scarring. This article intends to review the roles of TGF-beta in the formation of wound scarring, the possible strategies of antagonizing wound TGF-beta, and our preliminary results of scar gene therapy, which show that wound scarring can be significantly reduced by targeting wound TGF-beta.