Chemical synapses are heterogeneous junctions formed between neurons that are specialized for the conversion of electrical impulses into the exocytotic release of neurotransmitters. Voltage-gated Ca.sup.2+ channels play a pivotal role in this process as they are the major conduits for the Ca.sup.2+ ions that trigger the fusion of neurotransmitter-containing vesicles with the presynaptic membrane. Alterations in the intrinsic function of these channels and their positioning within the active zone can profoundly alter the timing and strength of synaptic output. Advances in optical and electron microscopic imaging, structural biology and molecular techniques have facilitated recent breakthroughs in our understanding of the properties of voltage-gated Ca.sup.2+ channels that support their presynaptic functions. Here we examine the nature of these channels, how they are trafficked to and anchored within presynaptic boutons, and the mechanisms that allow them to function optimally in shaping the flow of information through neural circuits. Voltage-gated calcium channels have an essential role in the regulation of neurotransmitter release. Dolphin and Lee describe here how advances in the techniques available to study presynaptic voltage-gated calcium channels have provided insight into their composition, trafficking, regulation and contributions to presynaptic function.