Virtually all excitable cells express plasma membrane voltage-gated Ca2+ channels (VGCCs) that transduce electrical activity into intracellular biochemical signals. Membrane depolarization triggers the opening of VGCCs to allow rapid influx of extracellular Ca2+, which, in turn, regulates numerous physiological processes: the release of neurotransmitters and neuropeptides, neuronal excitability and plasticity, gene expression, development as well as cell survival and death (Tsien and Wheeler, 1999). Studies of Ca2+ currents in dorsal root ganglion (DRG) neurons date back to the early days of VGCC research and in 1985 led to the functional discovery of N-type Ca2+ channel (Nowycky et al., 1985). Remarkably, only twenty years later, the N-type Ca2+ channel blocker Prialt®, also known as SNX111 or ziconotide, was approved in both United States and Europe to treat intractable pain. It is anticipated that additional treatment modalities will derive from further understanding of the contribution of multiple VGCCs to nociceptive processing, in both the normal and the disease setting.