Intra-aortic balloon pump (IABP) counterpulsation is the most widely used mechanical circulatory support device because of its ease of use, low complication rate, and fast manner of insertion. Its benefit is still subject of debate, and a considerable gap exists between guidelines and clinical practice. Retrospective nonrandomized studies and animal experiments show benefits of IABP therapy. However, recent large randomized trials do not show benefit of IABP therapy, which has led to a downgrading in the guidelines. In our view, this dichotomy between trials and practice might be the result of insufficient understanding of the prerequisites needed for effective IABP therapy, that is, exhausted autoregulation, and of not including the right patient population in trials. The population included in recent large randomized trials has been heterogeneous, also including patients in whom benefit of IABP could not be expected. The clinical condition in which most benefit is expected, that is persistent ischemia in acute ST-elevation myocardial infarction, is discussed in this review. In conclusion, this review aims to explain the physiological principles needed for effective IABP therapy, to reflect critically on the large randomized trials, and to solve some of the controversies in this field.