The first successful heart transplant by Christiaan Barnard in Cape Town, South Africa in 1967 can be regarded as the birth of the modern treatment of end-stage heart failure. This surgical heart failure treatment milestone led to global euphoria and unbelievable hope that heart failure could be healed, even though the first patient to receive a transplant survived only a few days. Managing immunosuppression proved to be problematic, with only a few substances available [42]. It was the introduction of the calcineurin inhibitor (CNI) cyclosporine A in 1982 in particular that helped raise the 3-year survival rate from about 40% to 70% [43]. Later developments in standardized pharmacological protocols and new immunosuppressive drugs for the induction and maintenance of permanent immunosuppression provided further insights and beneficial long-term effects. Thus, inhibition of the ‘mammalian target of rapamycin (mTOR)’ in combination with a CNI demonstrated favourable effects with less coronary allograft vasculopathy compared to standard treatment [44, 45]. Furthermore, CNI-free immunosuppression protocols demonstrated improved renal function in patients with a heart transplant and chronic renal failure compared to CNI-based protocols. This result might affect prognosis after the transplant, because CNI-related renal failure is a common problem after a cardiac transplant and a major cause of long-term morbidity [46, 47]. Also, graft preservation techniques and ex vivo perfusion (as discussed below) might contribute to the constantly improving long-term results.