Synaptic transmission starts with the release of neurotransmitters by exocytosis of synaptic vesicles. As a relatively simple organelle with a limited number of components, synaptic vesicles are in principle accessible to complete structural and functional genetic analysis. At present, the majority of synaptic vesicle proteins has been characterized, and many have been genetically analyzed in mice, Drosophila, and Caenorhabditis elegans. These studies have shown that synaptic vesicles contain proteins with diverse structures and functions. Although the genetic studies are as yet unfinished, they promise to lead to a full description of synaptic vesicles as macromolecular machines involved in all aspects of presynaptic neurotransmitter release.