For many years, astrocytes and oligodendrocytes were considered the inert partners of neurons in the central nervous system (CNS), but several recent studies have dramatically challenged this view. Glial cells express a large number of different voltage- and ligand-gated ion channels (Verkhratsky and Steinhauser. Brain Res Rev 32:380-412, 2000) as well as G-protein-coupled receptors (Verkhratsky et al. Physiol Rev 78:99-141, 1998)-machinery necessary to sense and respond to neuronal activity. These findings raised the fundamental question as to whether glial receptors are stimulated under physiological conditions, and what sorts of events are triggered by such activation. During the early 1990s, P. Haydon and colleagues made the seminal observation that [Ca(2+)](i) rises in cultured astrocytes are associated with the release of glutamate, which suggested that astrocytes respond to activation and play active modulatory roles in intercellular communication (Parpura et al. Nature 369:744-747, 1994). Subsequent studies performed in situ confirmed and extended this initial observation. In this review, we will focus specifically on the hippocampus and sum up evidence of bidirectional communication between astrocytes and neurons emerging from recent studies using acute slice preparations.