Voltage-dependent Ca2+ channels (VDCC) constitute a key element in neuronal communication, serving as transducers of membrane potential changes into intracellular Ca2+ transients that initiate many physiological events. The combination of patch-clamp techniques, ω-toxins, and molecular strategies has revealed a great heterogeneity of VDCCs in neurons. Marine toxins have been invaluable tools to recognize the role of each channel subtype in controlling the Ca2+-dependent exocytotic release of a given neurotransmitter. Some static or slow animals, both terrestrial and marine, have developed a distinctive repertoire of venom peptides that are used both as a defense mechanism and also to facilitate the immobilization and digestion of prey. Ca2+ in flux through VDCCs not only serves to generate an intracellular Ca2+ signal that can activate gene transcription, protein phosphorylation, neurotransmitter release, and other intracellular functions, but it also exerts a feedback regulation of the channel activity.