The quest for a practical total artificial heart (TAH) stems from the large number of patients with advanced heart failure, and the limited number of donor hearts available for transplantation. In this Perspectives article, Cohn et al. give their expert insight into the development of TAHs over the past 50 years. They describe the evolution from positive-displacement, pulsatile pumps to continuous-flow devices, and give their opinion on the most promising avenues for future innovation.