Extracorporeal membrane oxygenation (ECMO) is a form of cardiopulmonary bypass that is a mainstay of therapy in neonatal and pediatric patients with life threatening respiratory and/or cardiac failure. Historically, the use of ECMO in adults has been limited, but recent reports and technological advances have increased utilization and interest in this technology in adult patients with severe respiratory failure. As ECMO is considered in this critically ill population, patient selection, indications, contraindications, comorbidities, and pre-ECMO support are all important considerations. Once the decision is made to cannulate a patient for ECMO, meticulous multi-organ-system management is required, with a priority being placed on lung rest and minimization of ventilator-induced lung injury. Close monitoring is also necessary for complications, some of which are related to ECMO and others secondary to the patient's underlying degree of illness. Despite the risks, reports demonstrate survival > 70% in some circumstances for patients requiring ECMO for refractory respiratory failure. As the utilization of ECMO in adult patients with respiratory failure continues to expand, ongoing discussion and investigation are needed to determine whether ECMO should remain a "rescue" therapy or if earlier ECMO may be beneficial as a lung-protective strategy.