Surface active material is important in the function of both the infant and adult lung. In the premature infant, surfactant depletion results in the requirement for very high distending pressures to open alveoli. As a consequence, shunt, hypoxemia, and right ventricular dysfunction occur. Surfactant replacement, especially by the direct instillation approach, has been proven effective in improving clinical outcome under these circumstances. Problems with surfactant instillation include the "fluid bolus" effect and concerns about optimal distribution of the instilled material. Recent improvements in aerosol systems have created interest in using aerosol delivery to reduce the total dose of surfactant required to treat RDS. In adult acute lung injury, surfactant dysfunction, rather than depletion, is the problem. Simple phospholipid replacement strategies thus may not be effective. Instead, surfactant delivery strategies aimed at regional targeting with surfactants having the necessary associated proteins may be the goal in ARDS. In adults, several instillation trials are underway, but there is also a hope that an aerosol strategy might also be tried. The aerosol route may be particularly useful if a high-efficiency aerosol system (eg, one distal to an endotracheal tube) can be shown to be effective. Other surface active materials exist and there are small studies showing benefit when large instilled doses of these materials are given. These materials, however, have never been studied as aerosols.