Voltage-gated ion channels are well characterized for their function in excitability signals. Accumulating studies, however, have established an ion-independent function for the major classes of ion channels in cellular signaling. During the last few years we established a novel role for Kv2.1, a voltage-gated potassium (Kv) channel, classically known for its role of repolarizing the membrane potential, in facilitation of exocytosis. Kv2.1 induces facilitation of depolarization-induced release through its direct interaction with syntaxin, a protein component of the exocytotic machinery, independently of the potassium ion flow through the channel's pore. Here, we review our recent studies, further characterize the phenomena (using chromaffin cells and carbon fiber amperometry), and suggest plausible mechanisms that can underlie this facilitation of release.