Glutamatergic gliotransmission, that is the release of glutamate from perisynaptic astro-cyte processes in an activity-dependent manner, has emerged as a potentially crucial signal-ing pathway for regulation of synaptic plasticity, yet its modes of expression and function in vivo remain unclear. Here, we focus on two experimentally well-identified gliotransmit-ter patwhays: (i) modulations of synaptic release and (ii) postynaptic slow inward currents mediated by glutamate released from astrocytes, and investigate their possible functional relevance on synaptic plasticity in a biophysical model of an astrocyte-regulated synapse. Our model predicts that both pathways could profoundly affect both short-and long-term plasticity. In particular, activity-dependent glutamate release from astrocytes, could dramatically change spike-timing–dependent plasticity, turning potentiation into depression (and vice versa) for the same protocol.