Animal-derived surfactants containing SP-B and SP-C are more effective in vitro and in animal models than their synthetic counterparts, but are not as effective as unmodified, naturally occurring surfactant. In clinical trials involving newborn babies with respiratory distress syndrome (RDS) these short-term differences are reflected as improvements in gas exchange and lung function. Treatment with animal-derived surfactants results in fewer air leaks and lower neonatal mortality. The evidence is now strong enough to recommend routine use of animal-derived surfactants in very preterm infants with RDS. The newer generation of synthetic surfactants may be important in the future as they have the advantages of currently available animal products with the addition of better resistance to inactivation.