To assess the safety and efficacy of bioengineered skin substitutes in comparison with biological skin replacements and/or standard dressing methods in the management of burns, through a systematic review of the literature. Literature databases were searched up to April 2006, identifying randomised controlled trials. Twenty randomised controlled trials were included in this review. The numerous sub-group analyses and the diversity of skin substitutes limited the ability to draw any conclusions from it. However, the evidence suggested that bioengineered skin substitutes, namely Biobrane, TransCyte, Dermagraft, Apligraf, autologous cultured skin, and allogeneic cultured skin, were at least as safe as biological skin replacements or topical agents/wound dressings. The safety of Integra could not be determined. For the management of partial thickness burns, the evidence suggested that bioengineered skin substitutes, namely Biobrane, TransCyte, Dermagraft, and allogeneic cultured skin, were at least as efficacious as topical agents/wound dressings or allograft. Apligraf combined with autograft was at least as efficacious as autograft alone. For the management of full thickness burns, the efficacy of autologous cultured skin could not be determined based on the available evidence. The efficacy of Integra could not be determined based on the available evidence. Additional methodologically rigorous randomised controlled trials with long-term follow-up would strengthen the evidence base for the use of bioengineered skin substitutes.