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It has been passed already more than 20 years since it is thought to be pig-to-human xenotransplantation. However, the main 3 limitations; zoonosis, immunological rejection and ethical problems were still remained for xenotransplantation. The ethical issues are a matter to be resolved in the form of consideration slowly and importantly, also nationally and legally. A lot of scientist of the world are trying to solve the remaining limitations which were immune rejection and zoonosis. As the limitation of xenotransplantation, the zoonosis is a disease caused by viral bacterial parasites that can be transmitted to humans from animal (pig-to-human) at the same time. The best solution of this should be the germfree animal source. In other respects, about the immune rejection, there are 3 steps of immune rejection by the time of occurrence which are hyper-acute rejection, acute cellular/humoral rejection and chronic rejection. An alpha- 1,3-galactosyl transferase(GALT) KO pigs were produced and investigated for overcoming hyper-acute rejection in xenotransplantation by various research groups. After GALT which is thought to be the only factor of hyper-acute rejection from pig-to-human xenotransplantation, there were some unexpected results occurred by increasing nongal epitopes such as CMAH. Furthermore, not only complement regulatory proteins but also thrombomodulin (TBM), tissue factor pathway inhibitor (TFPI) and other coagulation factors were over-expressed in minipig are considered as candidate of modification genes to solve the acute vascular-humoral rejection problem. Other than that, to overcome the acute cellular rejection problem, the cellular immune activator/inhibitors such as CD47, IL-10, CTLA-4, CD80/86(B7) have been considered. Therefore, for successful xenotransplantation, the overexpression of several immune escaping genes on the base of GALT KO pig is considered to be the best solution and is currently on the way.