The vision to develop a mechanical blood pump to support or replace the failing human heart was originally proposed in the late 1950s by Dr DeBakey. Since then, a portfolio of durable devices has been demonstrated to effectively salvage patients with advanced heart failure and cardiogenic shock. Arguably, the most important advances have occurred in the development of left ventricular assist devices. However, there remains an important patient cohort not well served by devices that only support the failing left heart. Advances in total mechanical heart replacement have lagged behind left-sided devices, but a new generation of total artificial hearts is being refined and evaluated to realize the early vision to have an off-the-shelf solution for patients with univentricular or biventricular heart failure. This review is intended to define the patient populations better suited for the total artificial heart, explore management of this cohort, and examine some of the new technologies in various phases of development that may fill the gap in currently unmet clinical need.