Persistent or recurrent symptoms following carpal tunnel release surgery are an infrequent but challenging clinical problem. A thorough evaluation of these patients is mandatory and must confirm the accuracy of the original diagnosis and rule out the presence of concurrent conditions or disorders that may cause persistent symptoms that mimic carpal tunnel syndrome. If an alternative explanation of the patients' symptoms cannot be identified, and if conservative care is ineffective, then surgical treatment should be considered. Adequate exposure of the median nerve and carpal tunnel are mandatory. The general approach should include gentle mobilization of the nerve from adherent scar tissue and interposition of a biologic barrier between the nerve and surrounding tissues. No published data conclusively demonstrate that internal neurolysis provides superior results. Postoperative care should include early mobilization to encourage tendon and nerve gliding.