Close structural and functional interactions of astrocytes with synapses play an important role in brain function. The repertoire of ways in which astrocytes can regulate synaptic transmission is complex so that they can both promote and dampen synaptic efficacy. Such contrasting effects raise questions regarding the determinants of these divergent astroglial functions. Recent findings provide insights into where, when and how astroglial regulation of synapses takes place by revealing major molecular and functional intrinsic heterogeneity as well as switches in astrocytes occurring during development or specific patterns of neuronal activity. Astrocytes may therefore be seen as boosters or gatekeepers of synaptic circuits depending on their intrinsic and transformative properties throughout life.