Despite encouraging and improving results, organ transplantation is still hampered by a shortage of organs, chronic transplant loss, and a changed patient population. Liberal inclusion criteria for dialysis and/or renal transplantation and the increasing unwillingness to donate organs in some countries had led to a growing imbalance between the numbers of transplantations performed and patients on waiting lists. Until now, poorly understood chronic transplant dysfunction is responsible for a still unchanged graft loss of approximately 5% per year. The patient population has changed to include more multimorbidity and an increasing number of risk factors (age, diabetes mellitus, former [failed] transplantations, or preexisting cardiovascular diseases). The recommendation for a against dialysis or transplantation has become increasingly difficult for the responsible physician. Newly developed immunosuppressant drugs, an increasing consideration regarding living organ donation, or xenotransplantation in the future may solve this dilemma. New reflections and considerations about the ethical background of transplantation medicine are necessary.