Vagus nerve stimulation (VNS) is currently undergoing multiple trials to explore its potential for various clinical disorders. To date, VNS has been approved for the treatment of refractory epilepsy and depression. It exerts antiepileptic or antiepileptogenic effect possibly through neuromodulation of certain monoamine pathways. Beyond epilepsy, VNS is also under investigation for the treatment of inflammation, asthma, and pain. VNS influences the production of inflammatory cytokines to dampen the inflammatory response. It triggers the systemic release of catecholamines that alleviates the asthma attack. VNS induces antinociception by modulating multiple pain‐associated structures in the brain and spinal cord affecting peripheral/central nociception, opioid response, inflammation process, autonomic activity, and pain‐related behavior. Progression in VNS clinical efficacy over time suggests an underlying disease‐modifying neuromodulation, which is an emerging field in neurology. With multiple potential clinical applications, further development of VNS is encouraging.