Won-Suk Chung1,4, Katherine T. Baldwin2,4 and Nicola J. Allen3,4 1Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Yuseong-gu, Daejeon 34141, Korea 2Department of Cell Biology and Physiology and UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA 3Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA Correspondence: wonsuk.chungkaist.ac.kr; ktbaldwinmed.unc.edu; nallensalk.edu

↵4 These authors contributed equally to this work.

Astrocytes play an integral role in the development, maturation, and refinement of neuronal circuits. Astrocytes secrete proteins and lipids that instruct the formation of new synapses and induce the maturation of existing synapses. Through contact-mediated signaling, astrocytes can regulate the formation and state of synapses within their domain. Through phagocytosis, astrocytes participate in the elimination of excess synaptic connections. In this work, we will review key findings on the molecular mechanisms of astrocyte–synapse interaction with a focus on astrocyte-secreted factors, contact-mediated mechanisms, and synapse elimination. We will discuss this in the context of typical brain development and maintenance, as well as consider the consequences of dysfunction in these pathways in neurological disorders, highlighting a role for astrocytes in health and disease.