PURPOSE OF REVIEW: Xenotransplantation is an attractive alternative to allogeneic transplantation because of the intractable shortage of donor organs. The latest published developments in this area are discussed as well as recent publications regarding the continuing debates on the ethics of xenotransplantation and the safeguards that should be imposed to assure the minimization of risk to the patient and to human societies. RECENT FINDINGS: Several laboratories are concentrating on the development of genetically manipulated donor pigs in order to bypass the immunological barriers against transplantation of porcine organs and cells into humans. Preliminary experiments with these new pig strains suggest that this strategy has a high likelihood of success with respect to hyperacute rejection. Ethical considerations have been extended to the establishment of regulatory, legal, and ethical frameworks that will be necessary to minimize the risk of xenotransplantation to the recipients, their families, and to the worldwide community. SUMMARY: Xenotransplantation, because of the complexity of the medical, ethical and legal issues, will likely remain a controversial issue. If the scientific problems are solved, the decision to proceed with clinical application of this technique will depend on a collective decision guided by ethical, regulatory, and legal frameworks established by consensus. © 2006 Lippincott Williams & Wilkins.