Surfactant replacement therapy may have a role in the treatment of ARDS in children. The current studies suggest that rapid instillation of exogenous surfactant is more effective than slow tracheal instillation or aerosolized delivery. Studies suggest that exogenous surfactant given early in the development of ARDS is more effective than therapy provided late in the course of the disease. Natural surfactants appear to be more effective than artificial surfactants due to the presence of SP-B and SP-C, which prevent inhibition of the exogenous surfactant by the protein leakage into the alveolus that is characteristic of ARDS. Exogenous surfactant replacement therapy appears to be safe and well tolerated. A surfactant that can be delivered by aerosol would be useful since this is more easily tolerated by the patients, requires less surfactant, and would be more cost effective when compared with tracheal instillation. Aerosolized surfactant could be given to patients who have not yet required mechanical ventilation, thus potentially preventing the progression of the acute lung injury to respiratory failure. The recent failure of a large multi-center trial of aerosolized Exosurf for the treatment of sepsis-related ARDS72 may have been due to the failure of the delivery system as opposed to the surfactant used in the trial; therefore, further research into aerosol delivery systems is needed. There may be different responses to exogenous surfactant therapy by patients with ARDS of different etiologies, such as aspiration pneumonia, sepsis, or trauma. Well-planned placebo-controlled trials will be required to determine these differences. The data supporting the role of surfactant replacement for the treatment of ARDS in children is growing. However, before widespread use of surfactant is considered, a multi-center, placebo-controlled trial will be required to establish the safety and efficacy of surfactant replacement in such patients.