The success of allotransplantation has led to an increasing shortage of human organs from deceased donors. This crisis could be resolved by the use of organs from an anatomically suitable animal, such as the pig. The pig and human have, however, been evolving differently for approximately 80 million years, and numerous immunological and physiological barriers have developed that need to be overcome. Differences in carbohydrate epitopes on pig and human cells have been found to play a major role in some of the immunological barriers that have been identified to date. The rejection caused by the presence of galactose-α1,3-galactose (Gal) on the pig vascular endothelium and of natural anti-Gal antibodies in humans has recently been prevented by the breeding of pigs that do not express Gal, achieved by knocking out the gene for the enzyme α1,3-galactosyltransferase, which was made possible by the introduction of nuclear transfer/embryo transfer techniques. N-glycolylneuraminic acid (the so-called Hanganutziu-Deicher antigen) has been identified as another carbohydrate antigen present in pigs that may need to be deleted if xenotransplantation is to be successful, although some doubt remains regarding its importance. There remain other antipig antibodies against hitherto unidentified antigenic targets that may well be involved in graft destruction; their possible carbohydrate target epitopes are discussed. © 2005 Australasian Society for Immunology Inc.