Significant cutaneous sulfur mustard (HD) injuries can take several months to heal, necessitate lengthy hospitalizations, and result in significant cosmetic and/or functional deficits. Currently recommended treatments are not optimal or sufficiently aggressive to prevent or minimize HD-induced lesions, or to provide for speedy wound healing. We have formulated strategies for the development of improved therapies, with the aim of returning damaged skin to “normal” appearance and function in the shortest time. Before established HD injuries can be appropriately treated, assessment of the injuries must occur. Total body surface area of the injuries should be estimated, followed by a determination of injury depth. Accurate depth assessment is important, because it dictates how aggressive treatment needs to be to minimize or prevent cosmetic and functional deficits. Laser Doppler perfusion imaging and indocyanine green fluorescence imaging may prove to be very valuable tools in diagnosing depth of cutaneous HD injuries. Following assessment of injury, adequate wound debridement needs to be performed. Several studies have clearly demonstrated the advantages of debridement in improving the wound healing of cutaneous vesicant injuries. Powered dermabrasion and sharp surgical excision have proven efficacious. Laser debridement has been particularly successful. Enzymatic debridement may also prove to be efficacious. The most popular and effective agents for enzymatic debridement on the market today are collagenases and papain/urea combinations, which should be tested in an appropriate animal model for efficacy in debriding cutaneous HD injuries. Following wound debridement, an appropriate dressing will be needed to promote moist wound healing. Hydrocolloids, hydrogels, thin films, and silver-impregnated dressings should be considered. The use of skin substitutes to dress these wounds and temporarily restore the multiple functions of normal skin may be of substantial benefit in the management of cutaneous HD injuries. Skin substitutes are widely used in human thermal burns management, and can be (1) temporary or permanent, (2) epidermal, dermal, or composite, and (3) biologic or synthetic. Application of cultured epithelial allografts, autografts, or keratinocytes in suspension may also prove efficacious. Application of growth factors such as platelet-derived growth factor (PDGF) and keratinocyte growth factor (KGF) or “cosmeceutical” products designed for topical nutritional support may also be beneficial in improving wound healing following debridement. Application of topical negative pressure in the management of chronic wounds and burns has gained popularity in the last five years. Vacuum Assisted ClosureTM (V.A.C.®) may prove efficacious in significantly speeding the re-epithelialization process in cutaneous vesicant injury.