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More patients will accept regional blocks if these are performed during sedation or general anesthesia. This review discusses regional anesthesia in sedated or anesthetized patients.As complications of regional blocks are rare, regional anesthesia can be considered aswell-tolerated. Awake patients will notice only a minority of needle-to-nerve contacts, that renders the notion of a ‘live monitor’ obsolete. Using high-resolution ultrasound, the needle can be advanced to an extraepineural position for injection, thus strictly avoiding needle-to-nerve contact or intraepineural injection of local anesthetic. Rare cases of intoxication manifest more immediately when the patient is awake but some general anesthesia drugs reduce the seizure-inducing potency of local anesthetics, and hemodynamic signs of intoxication are also detectable under general anesthesia, allowing for faster cardiopulmonary resuscitation as the patient is anesthetized already.With the use of ultrasound guidance in skilled hands, it is a reasonable option to perform neuraxial and peripheral regional blocks in sedated or anesthetized patients. Performing the procedure safely and effectively requires an adequate level of experience with the specific block technique in question.