Several issues persist in clinical translation and application of cultured epithelial autografts during treatment of patients with massive burn injuries. The aim of this systematic review is to determine (1) current practice and trends in clinical application and (2) clinical efficacy of cultured epithelial autografts. A structured literature search was performed in Ovid MEDLINE from 1946 and Ovid EMBASE from 1974 until present. All published peer-reviewed randomized or non-randomized clinical studies, cohort studies, prospective, or retrospective series involving human application of cultured epithelial autografts in the setting of burn injury were included. From 7,267 studies initially identified, 77 studies were included in the analysis. In 96% (74/77) of these series, the sample size was less than 100 patients. In 76.6% (59/77) publications, average burn treated exceeded 40% total body surface area. Overall, cultured epithelial autograft take rates reported in the literature were inconsistent and varied significantly from 0 to 100%. There was a recent trend for co-application of cultured grafts with autologous skin grafts, achieving relatively high and consistent take rates of 73–96%. Results from cultured epithelial autograft application remained unpredictable. This technology remains an adjunct or biological dressing, and not an alternative to conventional split skin graft. However, it has contributed to wound closure and it has been life saving in selected circumstances. Skin tissue engineering should continue as the clinical need for skin replacement is foreseeable into the future.