Vagus nerve stimulation (VNS) can modulate vagal activity and neuro-immune communication. Human and animal studies have provided growing evidence that VNS can produce analgesic effects in addition to alleviating refractory epilepsy and depression. The vagus nerve (VN) projects to many brain regions related to pain processing, which can be affected by VNS. In addition to neural regulation, the anti-inflammatory property of VNS may also contribute to its pain-inhibitory effects. To date, both invasive and noninvasive VNS devices have been developed, with noninvasive devices including transcutaneous stimulation of auricular VN or carotid VN that are undergoing many clinical trials for chronic pain treatment. This review aimed to provide an update on both preclinical and clinical studies of VNS in the management for chronic pain, including fibromyalgia, abdominal pain, and headaches. We further discuss potential underlying mechanisms for VNS to inhibit chronic pain.