Abstract Heart transplantation (HTx) is considered the “gold standard” therapy of refractory heart failure (HF), but it is accessible only to few patients because of the paucity of suitable heart donors. On the other hand, left ventricular assist devices (LVADs) have proven to be effective in improving survival and quality of life in patients with refractory HF. The challenge encountered by multidisciplinary teams in dealing with advanced HF lies in identifying patients who could benefit more from HTx as compared to LVAD implantation and the appropriate timing. The decision-making is based on clinical parameters, imaging-based data and risk scores. Current outcome of HF patients supported by LVAD (2-year survival around 70%) is rapidly improving and leads the way to a new therapeutic strategy. Patients who have a low likelihood to gain access to the heart graft pool could benefit more from LVAD implantation (defined as bridge to transplantation indication) than from remaining on HTx waiting list with the likely risk of clinical deterioration or removal from the list because patients are no longer suitable for transplantation. LVAD has also demonstrated to be effective in patients who are not considered eligible candidates for HTx with a destination therapy indication. HTx should be reserved to those patients for whom the maximum clinical benefit can be expected, such as young patients with no comorbidities. Here we discuss the current listing criteria for HTx and indications to implant of LVAD for patients with refractory acute and chronic HF based on the guidelines and the practical experience of our center.