Devastating facial deformities can cause significant functional and psychosocial injury. Significant facial disfigurement can preclude meaningful human interaction. Allotransplantation of facial tissues for reconstruction of devastating deformities has become a clinical reality, with 15 transplants performed at various centers around the world. Restoration of aesthetics and functionality has been superior to that achieved by conventional reconstruction, without the morbidity of multiple surgeries. Unlike solid organ transplantation which can be life saving, facial transplantation is considered by many to be life enhancing, highlighting the ethical argument against justification of these procedures given the risks of lifelong immunosuppression. Meticulous patient selection is mandatory, and a multidisciplinary team approach is key for the program's success. The overriding goal of screening for candidacy is to identify and select subjects who have the best chance for a positive immunologic, functional, and quality-of-life outcome. This article reviews the pertinent considerations and screening approach for appropriate patient selection in facial tissue transplantation.