Background: To our knowledge, the role of neuron-astrocyte interaction in relation to Primary Astrocites (PA) has never been revised to the moment. Here we have summarized many of the aspects that we think should be taken into account when studying PA, along with the newest advances in the field. Objective: Given that the perinatal period is of particular importance for the developing brain, taking into account the continuous collaboration between astrocytes and neurons seems to be essential when studying PA pathogenic mechanisms and effects in the developing brain. As a fore said, the intricate relationship between these cell types plays a decisive role in the normal functioning of the developing CNS. Besides the crucial part they both play under healthy circumstances, there have been also great advances in identifying how this interaction works when brain insult occurs, influencing not only the development of brain injury in the perinatal period, but also the recovery. Conclusion: We have extensively revised several advantages that each cell type has, compensating the disadvantages of the other one, the molecular and signaling pathways that could be activated under HI conditions and that enable crucial collaboration during energy failure.