Over 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). Many reports indicate that the administration of GC decreases the incidence of RDS in the neonate delivered between 28 and 32 weeks and weighing less than 1500 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 them ambroxol and aminophylline. Ambroxol has been shown to reduce significantly RDS compared to placebo, without causing important adverse effects either on the mother or the baby. Our experimental studies on aminophylline have shown that the drug exerts only minor beneficial effects on fetal lung maturation and surfactant production. Recently we have evaluated the association of GC with inositol. The sugar alcohol dramatically affected pregnant rabbit fetal lung mechanisms, reducing GC-adverse effects such as decrease in lung DNA and protein content. In attempts to minimize the risk of neonatal RDS it is important (1) to identify pregnant women at risk for preterm labor; (2) to establish specific guidelines for the use of any prenatal drug to be administered for the prevention of RDS; (3) to assess fetal lung maturity; (4) to intensively monitor the fetus intrapartum; and (5) to prevent birth asphyxia.