AbstractNearly one‐half of the cells in a human brain are astrocytes, but the function of these little cells remains a great mystery. Astrocytes form an intimate association with synapses throughout the adult CNS, where they help regulate ion and neurotransmitter concentrations. Recent in vitro studies, however, have found that astrocytes also exert powerful control over the number of CNS synapses that form, are essential for postsynaptic function, and are required for synaptic stability and maintenance. Moreover, recent studies increasingly implicate astrocytes in vivo as participants in activity‐dependent structural and functional synaptic changes throughout the nervous system. Taken together, these data force us to rethink the role of glia. We propose that astrocytes should not be viewed primarily as support cells, but rather as cells that actively control the structural and functional plasticity of synapses in developing and adult organisms. © 2004 Wiley‐Liss, Inc.