Voltage-gated sodium ion channels are essential to maintain the excitability and activity of neurons and neuronal network. Several studies have been done to explore the basic properties of ion channels, their existence and physiological characteristics. Till date we know that 11 genes are responsible for encoding of 9 families of sodium channels (Nav 1.1 to Nav 1.9) and are classified according to varying degrees of sensitivity to Tetrodotoxin (TTX). These are localized in various sites such as skeletal muscles, central nervous system (CNS), cardiac muscles, and peripheral sensory neurons. Any aberration in its structure and function leads to various clinical pathologies such as channelopathies (where dysregulation in receptors are directly responsible for initiation and progression) and diseases contributing to dysregulation of expression of sodium channels cause various neurological disorders. In this chapter, we emphasize the composition, function, and regulation of sodium channels at the molecular level and the crucial role of sodium channels in the development and progression of various disease pathologies such as epilepsy, schizophrenia, familiar hemiplegic migraine and neuropathic pain.