Hypnosis is a technique that induces changes in perceptual experience through response to specific suggestions. By means of functional neuroimaging, a large body of clinical and experimental studies has shown that hypnotic processes modify internal (self-awareness) as well as external (environmental awareness) brain networks. Objective quantifications of this kind permit the characterization of cerebral changes after hypnotic induction and its uses in the clinical setting. Hypnosedation is one such application, as it combines hypnosis with local anesthesia in patients undergoing surgery. The power of this technique lies in the avoidance of general anesthesia and its potential complications that emerge during and after surgery. Hypnosedation is associated with improved intraoperative comfort and reduced perioperative anxiety and pain. It ensures a faster recovery of the patient and diminishes the intraoperative requirements for sedative or analgesic drugs. Mechanisms underlying the modulation of pain perception under hypnotic conditions involve cortical and subcortical areas, mainly the anterior cingulate and prefrontal cortices as well as the basal ganglia and thalami. In that respect, hypnosis-induced analgesia is an effective and highly cost-effective alternative to sedation during surgery and symptom management.