Astrocytes, a type of glial cells in the brain, are eukaryotic cells, and a hallmark of these are subcellular organelles, such as secretory vesicles. In neurons vesicles play a key role in signaling. Upon a stimulus-an increase in cytosolic concentration of free Ca(2+) ([Ca(2+)](i))-the membrane of vesicle fuses with the presynaptic plasma membrane, allowing the exit of neurotransmitters into the extracellular space and their diffusion to the postsynaptic receptors. For decades it was thought that such vesicle-based mechanisms of gliotransmitter release were not present in astrocytes. However, in the last 30 years experimental evidence showed that astrocytes are endowed with mechanisms for vesicle- and non-vesicle-based gliotransmitter release mechanisms. The aim of this review is to focus on exocytosis, which may play a role in gliotransmission and also in other forms of cell-to-cell communication, such as the delivery of transporters, ion channels and antigen presenting molecules to the cell surface.