In the last 4 decades, advances in neonatology have led to a significant increase in the survival of preterm infants. One of the biggest advances was the introduction of surfactant replacement therapy for the treatment of respiratory distress syndrome. This is the main cause of respiratory insufficiency in preterm infants and is one of the major causes of perinatal morbidity and mortality. Surfactant replacement therapy is already a well-investigated and established therapy in neonatology. However, surfactant replacement therapy has progressed and been refined over recent decades, especially with the increasing care for preterm infants born before 26 weeks' gestational age and the recent clinical focus on avoiding mechanical ventilation. Clinical evidence is evolving on new types of surfactant, surfactant dosages, co-medication given before, with, or after surfactant replacement, and new technical advances regarding the mode of administration.