BACKGROUND: Over the last decades, considerable progress has been made in the perinatal management of high-risk preterm neonates, changing the landscape of pathological conditions associated with neurological impairments. Major focal destructive lesions are now less common, and the predominant neuropathological lesion is diffuse white-matter damage in the most immature infants. Similarly, over the last few years, we have observed a trend towards a decrease in neurological impairment in the absence of treatments specifically aimed at neuroprotection. OBJECTIVES: We examined whether recent changes in treatment strategies in perinatal care during the perinatal period could have had an indirect beneficial impact on the occurrence of brain lesions and their consequences. METHODS: Thus, we reviewed the effects of the most common treatments administered during the perinatal period to the mother or to very preterm infants on brain damage and neurocognitive follow-up. RESULTS: Antenatal steroids and exogenous surfactant are the two main treatments capable of leading to neuroprotection in very preterm infants. Randomized controlled trials are currently investigating the effects of inhaled nitric oxide and erythropoietin, while antenatal magnesium sulphate and caffeine are also likely to provide some neuroprotection, but this needs to be further investigated. Finally, other common treatments against pain, haemodynamic failure and patent ductus arteriosus have conflicting or no effects on the developing brain. CONCLUSION: While specific neuroprotective drugs are still awaited, recent advances in perinatal care have been associated with an unexpected but significant decrease in the incidence of both severe brain lesions and neurological impairment.