Astrocytes regulate synaptic transmission and play a role in the formation of new memories, long-term potentiation (LTP), and functional synaptic plasticity. Specifically, astroglial release of glutamate, ATP, and cytokines likely alters the survivability and functioning of newly formed connections. Among these pathways, regulation of glutamate appears to be most directly related to the promotion of LTP, which is highly dependent on the synchronization of synaptic receptors through the regulation of excitatory postsynaptic potentials. Moreover, regulation of postsynaptic glutamate receptors, particularly AMPA receptors, is dependent on signaling by ATP synthesized in astrocytes. Finally, cytokine signaling is also implicated in regulating LTP, but is likely most important in plasticity following tissue damage. Despite the role of these signaling factors in regulating LTP and functional plasticity, an integrative model of these factors has not yet been elucidated. In this review, we seek to summarize the current body of evidence on astrocytic mechanisms for regulation of LTP and functional plasticity, and provide an integrative model of the processes.