Recently, xenotransplantation has been introduced in humans using genetically modified pigs in the United States. Although data of its results remains scarce, they undoubtedly harken the arrival of a new era. Our research on xenotransplantation began in 1986, demonstrating that the cause of hyperacute rejection was species-specificity in the complement system. Since then, the existence of xeno-glycoantigens has become clear, and α-Gal, H-D, and Sda have been identified and knocked out worldwide. Gradually, attention has started to be paid not only to the movement of adaptive immune cells but also to the movement of innate immune cells, and efforts are being made to establish methods to control them. Preclinical research has built on this fundamental research across the world, producing results that will allow clinical trials to begin. In addition to the importance of research, this work also highlights the legislative progress being made in Japan for the use of animal models in clinical research. With the production of several transgenic and knockout pigs, we are currently in the process of forming a consortium in Japan and pushing for legal reform in an effort to allow pigs to be used in clinical studies.