The release of neuromodulators, called gliotransmitters, by astrocytes is proposed to modulate neurotransmission and synaptic plasticity, and thereby cognitive functions; but they are also proposed to have a role in diverse neurological disorders. Two main routes have been proposed to ensure gliotransmitter release: non-exocytotic release from cytosolic pools through plasma membrane proteins, and Ca2+-regulated exocytosis through the fusion of gliotransmitter-storing secretory organelles. Regulated Ca2+-dependent glial exocytosis has received much attention and is appealing since its existence endows astrocytes with some of the basic properties thought to be exclusive to neurons and neuroendocrine cells. The present review summarizes recent findings regarding the exocytotic mechanisms underlying the release of two excitatory amino acids, L-glutamate and D-serine.