Sodium channel blocker insecticides (SCBIs) are a relatively new class of insecticides, with a mechanism of action different from those of other classes of insecticides that target voltage-gated sodium channels. These compounds have no effect at hyperpolarized membrane potentials, but cause a voltage-dependent, nearly irreversible block as the membrane potential is depolarized. The mechanism of action of SCBIs is similar to that of local anesthetics (LAs), class I anticonvulsants and class I antiarrhythmics. In this article, we review the physiological actions of these compounds on the whole animal, the nervous system and sodium channels, and also present the results from recent studies that elucidate the receptor site of SCBIs.