The burden of advanced heart failure is reaching epidemic proportions. Generally considered for cardiac transplantation, patients often cannot receive this therapy because of their advanced age, comorbidity or the scarcity of donors. Most transplants are concentrated in North America and Europe, with the average center performing fewer than 20 annual transplants. A search for nonbiological means of cardiac support has led to the advent of mechanical circulatory support (MCS), a concept now entrenched as a bridge to transplantation or, for those ineligible for transplantation, as lifetime therapy. In this review we discuss contemporary challenges posed by the changing epidemiology of cardiac transplant and MCS and outline the basis for an understanding of the future of this important therapeutic stance.