Calcium entry through neuronal voltage-gated calcium channels into presynaptic nerve terminal is a key step in synaptic exocytosis. In order to receive the calcium signal and trigger fast, efficient and spatially delimited neurotransmitter release, the vesicle-docking/release machinery must be located near the calcium source. In many cases, this close localization is achieved by a direct interaction of several members of the vesicle release machinery with the calcium channels. In turn, the binding of synaptic proteins to presynaptic calcium channels modulates channel activity to provide fine control over calcium entry, and thus modulates synaptic strength. In this chapter we summarize our present knowledge of the molecular mechanisms by which synaptic proteins regulate presynaptic calcium channel activity.