Cardiogenic shock (CS) still carries an unacceptably high mortality (30-60%), despite several therapeutic approaches; the SHOCK II trial questioned the benefit of intra-aortic balloon pump (IABP), while IMPRESS and CULPRIT-SHOCK trials confirmed heterogeneity in disease spectrum and patient selection for acute myocardial infarction-related CS requiring acute mechanical circulatory support (AMCS). The heterogeneity of devices employed as AMCS, including temporary micro-axial flow pumps (Impella), percutaneous bypass (TandemHeart), and extracorporeal life support (VA-ECMO), contributed to the actual dramatic scenario, where CS is defined clinically rather than hemodynamically. To date, the role of VA-ECMO is emerging as rapid strategy to mitigate mortality rates of severe refractory states, despite the lack of data regarding the best practices of management and flows control. VA-ECMO's flow represents the "dose" of treatment and higher flows are less tolerated percutaneously requiring, to prevent deleterious pulmonary edema and ventricular distention, additional approaches such as pulmonary, left atrial, or left ventricular unloading. Any efforts have to be directed to (1) determine adequate management of patients on VA-ECMO, (2) define the safer duration of VA-ECMO support, and (3) establish algorithms and techniques to predict and obtain stable weaning from ECMO or ensure fast transition to durable VAD and/or heart transplant.