Mu-Conotoxins (mu-CTX) are potent Na channel inhibitory peptides isolated from the venom of the predatory marine snail Conus geographus. Mu-CTXs exert their biological action by physically occluding the ion-conducting pore of voltage-gated Na (Na(v)) channels with a 1:1 stoichiometry in an all-or-none fashion. This article reviews our current knowledge of the mechanism of mu-CTX and the associated structural and functional insights into its molecular target--Na(v) channels.