Historically, the main goal in burn management was increasing the survival of severely burned patients by rapid debridement and early closure of burn wounds, consequently reducing the infection risk.1–4 However, in the last decennia, surgical emphasis has shifted from survival to “quality of survival,” especially by improving the residual scars and preventing contractures. Traditionally, surgeons divide burns into deep burns requiring surgical therapy, and superficial burns which heal spontaneous by re-epithelialization with minimal scarring. Nevertheless, there is a gray zone between those two groups in which therapeutic decision making is difficult. The final decision for surgery generally remains case and surgeon dependent, and will mainly depend on the total burned surface area.5 Wound closure can be obtained by diverse therapeutic modalities depending on the depth and healing potential of the burn wound.5 In this article, the main focus is on the surgical treatment of deep dermal and full thickness burns. We endeavor to give a comprehensive overview of the developments in skin substitutes, which is impossible without mentioning some alternative treatments. The current golden standard for deep burns is surgical debridement and closure with autologous split thickness skin grafts or “STG” (epidermis plus a thin layer of dermis). Nevertheless, donor areas are limited in extended burns, and the residual scars remain unsatisfactory due to the lack of dermis. A more aesthetical reconstruction can be obtained with full thickness skin grafts (epidermis and whole dermis), which are limited in dimension and can only be harvested in a few areas (groin, lower abdomen, etc.). Deep defects with exposed bone or neurovascular structures are currently treated with flap surgery, which gives an optimal aesthetical and functional result. Nevertheless, the severe donor-site morbidity, the technical difficulty, and sometimes severe complications limit its use mostly to secondary reconstructions. Consequently, alternative conservative and surgical treatments were developed to improve the healing and the quality of the residual scars.6 Several mechanisms are supposed to enhance healing: (i) providing the ideal wound environment (wound dressings, etc.), (ii) by assisting the intrinsic healing capacities (growth factors, cytokines, etc.), or (iii) by surgically replacing the damaged skin (“skin substitutes”), which also should reduce scarring in full thickness defects. A permanent skin substitute is a surgically fixated “long lasting” skin replacement, consisting of naturally occurring skin elements which become incorporated in the normal skin. The main issue of this definition is the longevity of a skin substitute, which seems to be mostly of commercial importance, where terms such as biological dressings, and permanent and temporary skin substitutes are used without a clear distinction. This literature review showed that technically similar products are commercialized as “permanent” by one company and as biological dressing by another. Therefore, we chose to divide all these products in the following categories, depending on the skin layer which is (temporary) replaced: epidermal, dermal and combined skin substitutes (or composite grafts; Fig. 1). In the future, a fourth group might need to be added: the combined skin substitute with a subcutaneous adipose layer.7 However, the difference between skin replacements and some wound dressings can be small. Wound dressings are intended for coverage instead of replacement, to optimize wound healing. Wound dressings can roughly be divided in dressings containing natural elements (such as honey ointments), synthetic dressings (such as silver-impregnated dressings), and biological dressings containing mammalian cells or cell-derived substances like collagens and growth factors (human donor skin). Synthetically manufactured, naturally occurring elements, such as cellulose membranes, are also synthetic dressings. Wound dressings are not considered as (permanent) skin substitutes because they are not incorporated in the healing wound. Some authors previously named some of these products “skin substitutes” (without mentioning “permanent”) but this only lead to confusing terminology. The most important biological dressing, used since the 1940s, is human donor skin or “cadaver skin.”8 It contains several beneficial factors (growth factors, cytokines, etc.), and it provides the ideal environment for healing. Because of better preservation techniques (glycerol or cryopreserved), the risk of infection transmission is minimized, and its rejection will be delayed up to 3 weeks to 5 weeks.8,9 One of the Submitted for publication May 18, 2009. Accepted for publication November 6, 2009. Copyright © 2010 by Lippincott Williams & Wilkins From the Department of Plastic Surgery and Burn Unit (N.B., A.P., H.H., J.V., S.M.), Ghent University Hospital; Faculty of Medicine and Health Sciences (N.B., H.H., J.V., H.B., S.I.B., S.M.), Ghent University, Ghent, Belgium; Department of Molecular Cell Biology and Immunology (C.D.R.), VUmc, Amsterdam, The Netherlands; Department of Dermatology (H.B.), Ghent University Hospital; Department of General Internal Medicine (S.I.B.), Ghent University Hospital; and Hogeschool Gent, Healthcare Department (S.I.B.), Ghent, Belgium. Address for reprints: Brusselaers Nele, MD, Department of Plastic Surgery, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium; email: Nele.Brusselaers@ugent.be.