Background: Voltage gated Na⁺ channels (VGSCs) contain a pore-forming α subunit and one or more β subunits. VGSCs are involved in a wide variety of pathophysiologies, including epilepsy, cardiac arrhythmia, multiple sclerosis, periodic paralysis, migraine, neuropathic and inflammatory pain, Huntington's disease and cancer. Increasing evidence implicates the β subunits as key players in these disorders. Objective: To review the recent literature describing the multifunctional roles of VGSC β subunits in the context of their role(s) in disease. Methods: An extensive review of the literature on β subunits. Results/conclusion: β subunits are multifunctional. As components of VGSC complexes, β subunits mediate signaling processes regulating electrical excitability, adhesion, migration, pathfinding and transcription. β subunits may prove useful in disease diagnosis and therapy.