Currently, the administration of surfactant to preterm infants with respiratory distress syndrome (RDS) mainly relies on intratracheal instillation; however, there is increasing evidence of aerosolized surfactant being an effective non-invasive strategy. We present a historical narrative spanning sixty years of development of aerosolization systems. We also offer an overview of the pertinent mechanisms needed to create and manage the ideal aerosolization system, with a focus on delivery, distribution, deposition, and dispersion in the context of the human lung. More studies are needed to optimize treatment with aerosolized surfactants, including determination of ideal dosages, nebulizer types, non-invasive interfaces, and breath synchronization. However, the field is rapidly evolving, and widespread clinical use may be achieved in the near future.