Neuron–glial interactions in the nervous system are of fundamental importance to many processes including neural migration, axon guidance, myelination and synaptic transmission. At synapses in the CNS, the physiological and structural relationship between neurons and astrocytes is particularly complex. The juxtaposition of astrocytic membranes with presynaptic and postsynaptic elements is important for regulating synaptic transmission and plasticity. Recent investigations demonstrate that the morphology of both neuronal and glial components show rapid, continuous structural remodeling in the hippocampus. These physical modifications are likely to have a significant functional impact upon neurotransmission and indicate that the remodeling of astrocytic morphology might be crucial for the dynamic regulation of the synapse and its microenvironment. In this review, we focus on the structural complexities of astrocyte–synapse interactions in the hippocampus and their implications for understanding synaptic physiology, behavior and disease.