Abstract: Astrocytes, the main population of glial cells in the central nervous system (CNS), exert essential tasks for the control of brain tissue homeostasis, supporting neuron and other glial cell activity from the developmental stage to adult life. To maintain the optimal functionality of the brain, astroglial cells are particularly committed to reacting to every change in tissue homeostatic conditions, from mild modifications of the physiological environment, a process called astrocyte activation, to the more severe alterations occurring in pathological situations causing astrocyte reactivity or reactive astrogliosis (Escartin et al., 2021). During these reactive states, astrocytes mount an active, progressive response encompassing morphological, molecular, and interactional remodeling, leading to the acquisition of new functions and the loss of others, whose intensity, duration, and reversibility are dependent on the nature of the stimulus and regulated in a contextspecific manner. Although astrogliopathology is a complex phenomenon including other pathophysiological entities beyond reactivity (atrophy, asthenia, loss of functions, aberrant phenotype, and death), decoding the still elusive molecular events involved in astrocyte reactivity is key to understanding how astrocytes contribute to CNS repair and realizing the full therapeutic potential of these capacities.