Astrocytes are key cellular partners to neurons in the brain. They play an important role in multiple processes such as neurotransmitter recycling, trophic support, antioxidant defense, ionic homeostasis, inflammatory modulation, neurovascular and neurometabolic coupling, neurogenesis, synapse formation and synaptic plasticity. In addition to their crucial involvement in normal brain physiology, it is well known that astrocytes adopt a reactive phenotype under most acute and chronic pathological conditions such as ischemia, trauma, brain cancer, epilepsy, demyelinating and neurodegenerative diseases. However, the functional impact of astrocyte reactivity is still unclear. During the last decades, the development of innovative approaches to study astrocytes has significantly improved our understanding of their prominent role in brain function and their contribution to disease states. In particular, new genetic tools, molecular probes, and imaging techniques that achieve high spatial and temporal resolution have revealed new insight into astrocyte functions in situ. This Research Topic provides a collection of cutting-edge techniques, approaches and models to study astrocytes in health and disease. It also suggests new directions to achieve discoveries on these fascinating cells.