Because the first generation of pulsatile-flow devices was primarily used to bridge the sickest patients to transplantation (bridge-to-transplant therapy), the current generation of continuous-flow ventricular assist devices qualifies for destination therapy for patients with advanced heart failure who are ineligible for transplantation. The first-generation devices were associated with frequent adverse events, limited mechanical durability, and patient discomfort due device size. In contrast, second-generation continuous-flow devices are smaller, more quiet, and durable, thus resulting in less complications and significantly improved survival rates. Heart transplantation remains an option for a limited number of patients only, and this fact has also triggered the discussion about the optimal timing for device implantation. The increasing use of continuous-flow devices has resulted in new challenges, such as adverse events during long-term support, and high hospital readmission rates. In addition, there are a number of device-related complications including mechanical problems such as device thrombosis, percutaneous driveline damage, as well as conditions such as hemolysis, infection, and cerebrovascular accidents. This review provides an overview of the evolution of mechanical circulatory support systems from bridge to transplantation to destination therapy including technological advances and clinical improvements in long-term patient survival and quality of life. In addition, recent changes in device implant strategies and current trials are reviewed and discussed. A brief glimpse into the future of mechanical circulatory support therapy will summarize the innovations that may soon enter clinical practice.