The history of the clinical use of mechanical circulatory assistance can be considered to encompass five different but overlapping eras. The first era began with the first experimental total heart replacement by Kolff and Akutsu in 1958, continued with the initiation of post-cardiotomy support of the failing heart by DeBakey in 1962, and ended with the first heart transplant by Barnard in 1967. The second era (1967–1971) involved the initial work with heart transplantation, including the first total artificial heart (TAH) replacement by Cooley as a bridge to transplant in 1969. This era ended because problems with immunosuppression made cardiac transplantation non-viable as a routine treatment for heart failure and confined its use to Stanford and other research centers. In the third era (1972–1982), the National Institutes of Health funded the research and development of pulsatile left ventricular replacement devices as destination therapy for heart failure. The fourth era (1982–2000) began with the revitalization of heart transplantation due to the introduction of cyclosporine as a more effective immunosuppressant for transplant recipients. This ultimately led to the successful use of pulsatile left ventricular assist devices (LVADs) both as a bridge to transplant and as destination therapy. The fifth era (2000–present) is that of the development and general application of effective and durable (>15 years) continuous-flow LVADs and improved TAHs.