Acute respiratory distress syndrome (ARDS) has become a well-recognized condition that can result from a number of different causes that lead to injury of the alveolar-capillary membrane. This results in high-permeability pulmonary oedema that disturbs the pulmonary surfactant system. In ARDS, the treatments available are still inadequate and morbidity, mortality, and costs remain unacceptably high. In the last 15 yrs, the morbidity and mortality rates of premature infants suffering from the respiratory distress syndrome (RDS) due to surfactant deficiency, have been reduced by exogenous surfactant therapy, and this treatment is now routinely used in most neonatal intensive care units. At this moment, only a few case reports and results of limited clinical pilot studies are available, in which patients with ARDS are treated with exogenous surfactant. Although the results from these studies are not consistent, the best results have been seen in patients treated with high concentrations or multiple doses of surfactant. It has been suggested that the increased permeability changes, along with the inflammatory response, lead to accumulation of plasma components in the alveolar space, causing inhibition of the instilled surfactant in a dose-dependent way. Thus, for treatment of ARDS, a high concentration of surfactant is required to overcome the inhibitory effect of plasma components. However, a few questions remain unanswered, including: When should surfactant treatment start? Which dosage? Of which type of surfactant? Which method of administration should be used, in combination with which type of ventilatory support, etc.?