A variety of different isoforms of voltage-sensitive Na⁺ channels have now been identified. The recent three-dimensional analysis of Na⁺ channels has unveiled a unique and unexpected structure of the Na⁺ channel protein. Na⁺ channels can be classified into two categories on the basis of their amino acid sequence, Na_V1 isoforms currently comprising nine highly homologous clones and Na_X that possesses structure diverging from Na_V1, especially in several critical functional motifs. Although the functional role of Na_V1 isoforms is primarily to form an action potential upstroke in excitable cells, recent biophysical studies indicate that some of the Na_V1 isoforms can also influence subthreshold electrical activity through persistent or resurgent Na⁺ currents. Na_V1.8 and Na_V1.9 contain an amino acid sequence common to tetrodotoxin resistant Na⁺ channels and are localized in peripheral nociceptors. Recent patch-clamp experiments on dorsal root ganglion neurons from Na_V1.8-knock-out mice unveiled an additional tetrodotoxin-resistant Na⁺ current. The demonstration of its dependence on Na_V1.9 provides evidence for a specialized role of Na_V1.9, together with Na_V1.8, in pain sensation. Although Na_X has not been successfully expressed in an exogenous system, recent investigations using relevant native tissues combined with gene-targeting have disclosed their unique “concentration”-sensitive but not voltage-sensitive roles. In this context, these emerging views of novel functions mediated by different types of Na⁺ channels are reviewed, to give a perspective for future research on the expanding family of Na⁺ channel clones.