Elucidating the role of astrocytes in brain physiology and pathology requires the access to specific tools, which unambiguously target these glial cells. Optogenetics and chemogenetics (designer receptors exclusively activated by designer drugs [DREADDs], engineered G-protein-coupled receptors activated by inert drugs) are revolutionary techniques that have significantly advanced our understanding of neuron–astrocyte interactions in the central nervous system. By enabling precise manipulation of astrocyte activity using light or engineered receptors, these methods allow to dissect the complex signaling pathways established between neurons and astrocytes. While optogenetics facilitates real-time observation of astrocytic responses to neuronal activity, revealing their dynamic contributions to brain homeostasis, chemogenetics has contributed to enhance our understanding of the functional roles of astrocytes in different neurological disorders. Together, these techniques provide invaluable insights into the cellular mechanisms underlying brain function and pathology, paving the way for novel therapeutic strategies targeting neuron–astrocyte communication.