Acute respiratory distress syndrome (ARDS) has many underlying causes and carries an overall mortality of 40 to 60%. For those patients with severe ARDS who have a predicted mortality of 80 to 100%, extracorporeal life support (ECLS) can provide an extraordinary means of support. We recently demonstrated a survival to hospital discharge of 52% in this subset of patients. ECLS is capable of providing full respiratory and cardiac support, allowing time for the patient to recover from the underlying disease process. Additionally, ventilator settings are reduced to “rest” settings, avoiding the consequences of ventilator-induced lung injury that can contribute to a worse outcome. Systemic heparinization is a mainstay of ECLS therapy because of platelet activation in the circuit. Mechanical complications and significant bleeding can occur in up to one quarter of patients, requiring close attention and prompt intervention should they occur. Although not currently in clinical practice, liquid ventilation using perfluorocarbons to provide gas exchange in the lungs is a potentially useful adjunct in the management of severe respiratory failure.