Heart failure represents an increasing health problem in the United States that is associated with significant morbidity, mortality, and healthcare costs. It is estimated that more than 6 million Americans experience heart failure. Patients with end-stage heart failure have a very high 1-year mortality, and they have limited options for long-term management. This includes heart transplantation and durable mechanical circulatory support implantation. Due to limited donor availability, there is an increasing demand for mechanical circulatory support devices such as left ventricular assist device and total artificial heart, as these devices are becoming more viable long-term options. The postoperative ICU care of patients with mechanical circulatory support is complex and requires a multidisciplinary approach among the healthcare team. Due to the complexity of these patients, an in-depth understanding of the cardio-pulmonary pathophysiology and meticulous attention to detail from the healthcare team is required. A systematic and goal directed approach to the immediate post-implant period, focused on hemodynamic stability, hemostasis, respiratory function, acid base management, anticoagulation, nutrition, psychosocial support, infection prevention, and comprehensive patient support, is crucial in order to insure best patient outcomes.