Clark and Gollan demonstrated impressively in 1966 the ability of perfluorchemicals (PFCs) to transport oxygen and to provide gas exchange across the alveolar capillary membrane. PFCs are used for two major medical indications: as artificial blood substitutes and as a medium for liquid ventilation. The PFC perflubron is additionally used as a contrast medium for diagnostic radiologic procedures. For the intravenous application perfluorocarbons have to be emulgated in phospholipids for the intrapulmonary application the sterile pure solution is used. Liquid ventilation can either be performed by a method known as total liquid ventilation (TLV), in which a device is utilised to ventilate with perfluorocarbon the previously perfluorocarbon-filled lung, or as partial liquid ventilation (PLV) in which a conventional mechanical gas ventilator is used to gas ventilate the partially perfluorocarbon-filled lung. A number of studies have demonstrated the efficacy of perfluorocarbon liquid ventilation in improving gas exchange and pulmonary function in a number of animal species in the setting of acute respiratory failure. In 1989 Greenspan reported on the first human liquid ventilation experience in a neonate. More recently human experiences for neonatal, paediatric and adult patients with acute lung injury have been reported. Since 1995 an FDA-approved study to examine the efficacy of PLV in severe respiratory failure in patients of all ages has been undertaken in the United States. The number of PLV-treated patients is still small; if PLV demonstrates its efficacy even in the ongoing human studies, it might be a very effective additional tool for treating severe acute lung injury.