The history of cardiac transplantation is an intriguing story which started as a clinical experiment over four decades ago resulting in depressingly poor results to the point that the procedure risked abandonment as futile therapy. An era of renaissance emerged coincident with the introduction of cyclosporine-based immunosuppression evolving into an era where cardiac transplantation was regarded as the primary and “gold standard” therapy for end-stage heart disease. No doubt other factors and experience played into this development. Cardiac transplantation now, however, has entered quite a different era as a result of the considerable imbalance between the number of available donor hearts and the much greater number of potential recipients. Although long-term survival after cardiac transplantation has improved dramatically, the imperfections of current immunosuppression and the consequence of chronic rejection manifesting as coronary allograft vasculopathy continue to limit the long-term effectiveness of this therapy. In this present time, cardiac transplantation is but one of many surgical and nonsurgical alternatives for patients with end-stage heart disease. The challenge in this era is the accurate assignment of one or more therapies for an individual patient to produce the maximal benefit in terms of life expectancy and quality of life. The appropriate assignment of therapy for an individual patient is predicated upon the generation of patient-specific (which implies risk adjusted) time-related survival estimates for these various therapies, but currently the widespread application of this process remains elusive.