BACKGROUND/AIM: Facial transplantation is a revolutionary procedure developed recently, which is indicated if autologous transfers fail to restore human appearance. More than 30 patients have undergone facial transplantation in different centers worldwide. Here, we provide an update on its main anatomical, surgical, immunological, ethical, and follow-up aspects. We also provide innovative perspectives of regenerative medicine and tissue engineering that could hold promise for this emerging surgical field. METHODS: Through careful review of the anatomical, surgical, and tissue-engineering literature, we documented the main aspects of this innovative surgical procedure and its potential improvements in regenerative plastic surgery. RESULTS: Compatibility for the major blood groups (ABO) and human leukocyte antigen system between donor and recipient is critical to transplantation success. Major complications are tissue rejection and side effects of immunosuppression. The functional outcomes of facial transplantation are encouraging, with slow recovery of motor and sensory functions. Psychological impact on the family of the donor and recipient is essential for the success of facial transplantation. CONCLUSIONS: Uncertainty of long-term outcomes, immunosuppression-related concerns and ethical debates limit worldwide application of facial allotransplantation. However, in selected patients it is a unique reconstruction method with promising outcomes. Recent developments in regenerative medicine open a new frontier for application of patient-tailored, biocompatible and engineered reproductions of the various anatomical components of the face, and their application to transplant technology. Further research in transplant immunology, survival and conservation of grafts, and regenerative treatments of lesioned and/or transplanted tissues hold the key to advances in this emerging surgical option.