The idea of replacing 17beta-oestradiol (E2) and progesterone (P) in preterm infants is based on the observation that during pregnancy E2 and P plasma concentrations rise in the mother and the fetus by a factor of 100. Disruption of the placental supply of these hormones is a physiological event for an infant delivered at term. A preterm infant is deprived from this supply at an earlier developmental stage. In vitro and in vivo data are discussed, and they highlights the potential benefit of E2 and P on the development of different organ systems. The postnatal replacement of E2 and P has the aim of maintaining in utero plasma concentrations. In the first randomized clinical study in 30 extremely preterm infants, E2 and P were replaced postnatally for a total of 6 weeks. With a median intravenous replacement of 8.4 micromol/kg/day of E2 (4.2-22.9) and 67.4 micromol/kg/day of P (35.7-87.0), plasma levels of E2 and P were maintained within the intrauterine reference values of 7.3-22.0 nmol/L and 0.95-1.9 micromol/L, respectively. Three- to sixfold higher dosages were needed via the transepidermal route. Trends towards an improved postnatal bone mineral accretion and a reduced incidence of chronic lung disease were found. Further studies are warranted to clarify the potentially important role of E2 and P for the postnatal development of an extremely preterm infant.