It has been nearly three decades since the identification of the Drosophila Sodium Channel 1 (DSC1) gene from Drosophila melanogaster. The orthologs of the DSC1 gene have now been identified in other insect species including BSC1 from Blattella germanica. Functional analyses of DSC1/BSC1 channels in Xenopus oocytes reveal that DSC1 and BSC1 encode voltage-gated cation channels that are more permeable to Ca(2+) than to Na(+). Genetic and electrophysiological analyses show that knockout of the DSC1 gene in D. melanogaster causes behavioral and neurological modifications. In this review, we summarize major findings from recent studies and highlight a unique role of the DSC1 channel, distinct from that of the sodium channel, in regulating membrane excitability and modulating toxicity of pyrethroid insecticides.