Xenotransplantation is viewed as the most promising way to overcome the problems of shortage of donor organ. It can be exploited from rapidly expanding capabilities in genetic engineering for xenotransplantation. The major immunological hurdle to tissue or organ transplantations between phylogenetically-distant individuals is humoral immunity. In particular, immonupathologic effecs mediated by the reaction of natural antibodies and complement of recipient with graft endothelium in the donor organ cause xenograft rejection. Nevertheless, the phenomenon called "accomodation" that will occur immunologically may allow long survival of xenografts. In this review, immunologic hurdles to xenotransplantation and studies for overcoming the consequences of these will be discussed.