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Mutations in Na<jats:sub>v<\/jats:sub>channels are implicated in a wide variety of inherited pathologies, including cardiac conduction diseases, myotonic conditions, epilepsy and chronic pain syndromes. Drugs active against Na<jats:sub>v<\/jats:sub>channels are used as local anaesthetics, anti-arrhythmics, analgesics and anti-convulsants. The Na<jats:sub>v<\/jats:sub>channels are composed of a pore-forming \u03b1 subunit and associated \u03b2 subunits. The \u03b2 subunits are members of the immunoglobulin (Ig) domain family of cell-adhesion molecules. They modulate multiple aspects of Na<jats:sub>v<\/jats:sub>channel behaviour and play critical roles in controlling neuronal excitability. The recently published atomic resolution structures of the human \u03b23 and \u03b24 subunit Ig domains open a new chapter in the study of these molecules. 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