Mortality from the adult respiratory distress syndrome (ARDS) and the infant respiratory distress syndrome remains high despite numerous interventions and modalities. Perfluorocarbons (PFC) are inert liquids that can dissolve large amounts of oxygen and carbon dioxide and can be used as respiratory media. Partial liquid ventilation uses PFC to partially fill the lungs of patients with ARDS to improve gas exchange and support them. Studies in animals and humans (mostly neonates) using perflubron, which is currently the only PFC approved for clinical use, have shown that they are safe and effective in improving oxygenation. In this article the rationale of the technique, its historical background, and animal and clinical data to date are reviewed.