Extracorporeal membrane oxygenation support for respiratory failure in the intensive care unit continues to have an expanded role in select patients. While acute respiratory distress syndrome remains the most common indication, extracorporeal membrane oxygenation may be used in other causes of refractory hypoxemia and/or hypercapnia. The most common configuration is veno-venous extracorporeal membrane oxygenation; however, in specific cases of refractory hypoxemia or right ventricular failure, some patients may benefit from veno-pulmonary extracorporeal membrane oxygenation or veno-venoarterial extracorporeal membrane oxygenation. Patient selection and extracorporeal circuit management are essential to successful outcomes. This narrative review explores the physiology of extracorporeal membrane oxygenation, indications and contraindications, ventilator management, extracorporeal circuit management, troubleshooting hypoxemia, complications, and extracorporeal membrane oxygenation weaning in patients with respiratory failure. As the footprint of extracorporeal membrane oxygenation continues to expand, it is essential that clinicians understand the underlying physiology and management of these complex patients.