The clinical management of patients on extracorporeal membrane oxygenation should be standardized and follow clear guidelines or protocols. However, due to the diversity of cannulation strategies and the complex situations that extracorporeal membrane oxygenation is now used in, each extracorporeal membrane oxygenation program has developed its own clinical management strategies. These vary widely across the globe. Extracorporeal membrane oxygenation provides partial or complete support of ventilation and oxygenation, as well as univentricular or biventricular support of myocardial function, either individually or in combination. High-flow extracorporeal membrane oxygenation can also provide circulatory support in profound vasoplegic shock. Improvements in technology and greater understanding of disease pathophysiology, coupled to refinements in technology, which lessen the adverse interaction between the circuit and the patient, all contribute to fewer mechanical and patient complications on extracorporeal membrane oxygenation. Earlier and more appropriate use of extracorporeal membrane oxygenation has been associated with improved patient outcomes. These clinical management strategies are reviewed in this article, part of the Pediatric Cardiac Intensive Care Society/Extracorporeal Life Support Organization Joint Statement on Mechanical Circulatory Support.