In the last 10 years the strategy for the prevention of neonatal respiratory distress syndrome (RDS) has been directed towards the acceleration of fetal lung maturity in utero by means of drugs administered to the mother, the most thoroughly investigated being glucocorticoids (GC), and to the development of surfactant substitutes for the treatment of surfactant deficiency at birth or following the development of RDS. GC decreases the incidence of RDS in the neonate delivered between 28 and 32 weeks and weighing less than 1,500 g. The type of GC and the drug delivery interval are critical. Harmful potential side effects of GC have led to the testing of other drugs capable of accelerating fetal lung maturity, among which are ambroxol and aminophylline. Ambroxol has been shown to significantly reduce RDS compared to placebo without causing important adverse effects in either mother or baby. Our experimental studies on aminophylline have shown that the drug exerts only minor beneficial effects on fetal lung maturation and surfactant production. We have evaluated the association of GC with inositol. The sugar alcohol administered to the mother dramatically affected fetal lung mechanics, reducing GC adverse effects such as the decrease of lung protein content. More recently supplementary surfactant instilled into the trachea has been shown to improve oxygenation of premature babies and to reduce the severity of RDS.