SNARE proteins constitute the minimal machinery needed for membrane fusion. SNAREs operate by forming a complex, which pulls the lipid bilayers into close contact and provides the mechanical force needed for lipid bilayer fusion. At the chemical synapse, SNARE-complex formation between the vesicular SNARE VAMP2/synaptobrevin-2 and the target (plasma membrane) SNAREs SNAP25 and syntaxin-1 results in fusion and release of neurotransmitter, synchronized to the electrical activity of the cell by calcium influx and binding to synaptotagmin. Formation of the SNARE complex is tightly regulated and appears to start with syntaxin-1 bound to an SM (Sec1/Munc18-like) protein. Proteins of the Munc13-family are responsible for opening up syntaxin and allowing sequential binding of SNAP-25 and VAMP2/synaptobrevin-2. N- to C-terminal “zippering” of the SNARE domains leads to membrane fusion. An intermediate, half-zippered, state represents the “primed” vesicle, which is ready for release when C-terminal SNARE assembly is triggered by synaptotagmin. Following fusion, the SNAREs are recycled by the action of the AAA-ATPase NSF (N-ethylmaleimide-sensitive factor). In recent years, the lipid requirements for the SNARE mechanism have been scrutinized, and roles for the “noncanonical” SNAREs in the synapse are emerging, yet much remains to be learned about the spatial and temporal regulation of fusion.