An important aspect of Na+ channel regulation is their distribution on neuronal membranes within the nervous system. The complexity of this process is brought by the molecular diversity of Na+ channels and differential regulation of their distribution. In addition, Na+ channel localization is a highly dynamic process depending on the status of the cell in vitro, and (patho)physiological condition of the organism in vivo. Nonetheless, the pharmacological manipulation of Na+ channel distribution should be possible and will hopefully bring safer and more-potent medicines in the future.