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Surfactant homeostasis is disrupted in various pulmonary disease states, and exogenous surfactant therapy has been proposed as a treatment to improve lung function and recovery. Although this therapy has demonstrated clinically significant benefit in neonatal respiratory distress syndrome, for adult patients with acute respiratory distress syndrome (ARDS), the evidence is inconclusive. To understand the potential shortcomings of past trials and potential opportunities for more effective exogenous surfactant use in ARDS, we review in detail past trials and literature involving exogenous surfactant therapy in adult patients with ARDS. We assess various factors that may have impacted trial results and propose potential solutions and areas for future research. 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