The article provides an overview of the actions of S100B, a calcium-binding protein, on glial and neuronal cells in the developing brain. S100B is expressed in various glial cells, selected neuronal populations, and peripheral cells, and its expression varies across different regions of the brain during development in humans, mice, and rats. The review highlights S100B's roles in the differentiation, growth, and maturation of astrocytes, oligodendrocytes (OL), and the stimulation of dendritic development in serotonergic and cerebellar neurons. It also discusses the association between changes in S100B expression and neurodevelopmental alterations, such as impaired neurite outgrowth, neuronal migration, and altered radial glial cell morphology, which can lead to functional disturbances like slower weight gain and impaired spatial learning. The article emphasizes the importance of S100B in maintaining the integrity of the blood-brain barrier and modulating synaptic plasticity and memory. Additionally, it explores the spatiotemporal distribution of S100B during brain development and its role in glial and neuronal development, including its effects on astrocyte and OL maturation, and its trophic actions on serotonergic neurons. The review concludes by discussing how modifications in S100B expression, such as those caused by prenatal exposure to drugs or maternal pathology, can lead to neurodevelopmental changes.The article provides an overview of the actions of S100B, a calcium-binding protein, on glial and neuronal cells in the developing brain. S100B is expressed in various glial cells, selected neuronal populations, and peripheral cells, and its expression varies across different regions of the brain during development in humans, mice, and rats. The review highlights S100B's roles in the differentiation, growth, and maturation of astrocytes, oligodendrocytes (OL), and the stimulation of dendritic development in serotonergic and cerebellar neurons. It also discusses the association between changes in S100B expression and neurodevelopmental alterations, such as impaired neurite outgrowth, neuronal migration, and altered radial glial cell morphology, which can lead to functional disturbances like slower weight gain and impaired spatial learning. The article emphasizes the importance of S100B in maintaining the integrity of the blood-brain barrier and modulating synaptic plasticity and memory. Additionally, it explores the spatiotemporal distribution of S100B during brain development and its role in glial and neuronal development, including its effects on astrocyte and OL maturation, and its trophic actions on serotonergic neurons. The review concludes by discussing how modifications in S100B expression, such as those caused by prenatal exposure to drugs or maternal pathology, can lead to neurodevelopmental changes.