Neurogenesis requires the coordinated interplay between different cell types within the specialized microenvironment of the neurogenic niche. An important role is played by glia which, among their homeostatic roles, also include modulation of neural stem cells and their progeny.We will share and discuss recent molecular, biochemical and pharmacological data supporting an important role of astroglial cells in the modulation of neurogenesis under both physiological and pathological conditions, including aging and neurodegeneration. Particularly, focus will be on the role of astrocytes and their secretome as active contributors in the balance between quiescence and self-renewal of Neural Stem/Progenitor Cells and in the regulation of their differentiation programs to generate new neurons. Novel data about the role of astrocyte-derived soluble and matricellular molecules including CHI3L1 and thrombospondin-1, respectively, and their receptors/signalling pathways will be disclosed with specific relevance to their deregulation in aging, in animal models of Alzheimer’s disease and Down Syndrome and to their potential as novel pharmacological targets.