Objective:Disruption of smooth intrauterine brain development is a significant consequence of premature birth that may lead to adverse neurological outcomes. Although noteworthy progress has been made in the management of prematurity, the rates of neonatal morbidity and neurodevelopmental disorders remain high, underlining the need to find clinical practices that particularly protect the central nervous system. Aim:To identify recent articles regarding pharmacological and non-pharmacological brain-focused clinical practices (BFCP) for premature neonates at high risk of neuronal injury. Material and methods:We did an extensive search of PubMed and Google Scholar for relevant research published between 2000 and 2020. Results:Nineteen full-length original research papers fulfilled the inclusion criteria and were selected for the purpose of the present review. Non-pharmacological BFCP intend to improve the neonate's experience in the NICU environment and can be applied by a multidisciplinary team, while pharmacological ones are related to novel molecules that aim to quell apoptosis and inflammation or promote neurogenesis. Conclusion:In the future, a combination of pharmacological and non-pharmacological BFCP might be considered as the most promising protection and/or treatment provided in clinical practice to premature neonates at high risk of neuronal injury.