On 3 December 1967, Christiaan Barnard performed the first heart transplantation in the world at Groote Schuur Hospital in Cape Town, South Africa. In the succeeding months, heart transplantations in the USA, Asia and Europe followed. On 14 April 1969, Åke Senning successfully accomplished the first heart transplantation in Switzerland at the former Cantonal Hospital in Zurich. In the summer of 1969, he undertook a second heart transplantation. Although the surgical procedure went well technically, both patients died within weeks to months after transplantation. Causes of death were infection in the first and rejection in the second patient. Senning’s colleagues around the world had similar experiences. Survival after heart transplantation was unacceptably low. The heart transplant community recognised the lack of knowledge about immunological processes and appropriate immunosuppressive regimens as underlying reason for the early deaths. Most transplant centres decided to refrain from heart transplantation until sufficient immunological insight became available. After the introduction of the new immunosuppressive drug ciclosporin into the clinic and the availability of tools to monitor rejection in the early 1980s, heart transplant programmes were restarted all over the world. The legal recognition of brain death allowed procurement of donor hearts without exposure to warm ischaemia, and the principle of cold storage enabled prolongation of ischaemia time and acceptance of donors in distant hospitals, resulting in enlargement of the donor pool. In Switzerland, Marko Turina resumed heart transplantation in 1985 at Senning’s former workplace in Zurich. The number of heart transplants in Switzerland and in the world grew rapidly because the outcome markedly improved. Particularly over the long-term, survival in Zurich surpassed the outcome worldwide. Zurich created internationally recognised milestones such as transplantation of patients with grown-up congenital heart disease, the implementation of the bicaval instead of the right atrial anastomosis during the transplant procedure and the dual transplantation of one heart. Since the middle of the 1990s, however, the number of heart transplants has plateaued, mainly because of donor shortage. The current era is characterised by efforts to increase the number of donors. The utilisation of marginal donors, the change from informed to presumed consent for organ donation and donation after cardiocirculatory-determined death have been proposed to augment the donor pool.