Exogenous surfactant is currently being tested as a therapeutic modality for patients with acute respiratory distress syndrome (ARDS). Animal studies have shown that several factors may influence the efficacy of this treatment modality. These factors include the surfactant delivery method used (instillation vs. aerosolization), the timing of surfactant treatment over the course of injury, the specific surfactant preparation used, and the dose of surfactant administered. Each of these factors alone and together may influence the interaction of the exogenous surfactant with the host's alveolar environment. This, in turn, may dictate how a specific patient responds to a particular surfactant treatment strategy. It is suggested that patients at an early stage of lung injury will benefit from aerosolized exogenous surfactant whereas large quantities of an instilled exogenous surfactant may be necessary at later stages of injury. Future studies will clarify how a specific surfactant treatment strategy should be chosen for an individual patient with ARDS.