Xenotransplantation using pigs offers the prospect of an unlimited number of organs and cells for clinical transplantation. A major step forward has been achieved with the introduction of pigs homozygous for alpha1,3-galactosyltransferase gene-knockouts that do not express the major antigenic target for primate antipig antibodies (i.e., Galalpha1,3Gal). Heterotopic heart transplants have survived for 2-6 months in baboons. However, other immune and pathophysiologic barriers remain, including: i) anti-non-Gal antibodies and cells of the innate immune system; and ii) thrombogenesis associated with incompatibilities in the coagulation-anticoagulation systems of pig and primate. Further genetic modification of the organ-source pig to overcome these barriers is being undertaken.