Carpal tunnel syndrome (CTS) is 1 of the most common peripheral nerve entrapment disorders. Osteopathic manipulative medicine can be invaluable in diagnosing and managing CTS. Combined with a patient’s history and a standard physical examination, an osteopathic structural examination can facilitate localizing the nerve entrapment, diagnosing CTS, and monitoring the disease process. Osteopathic manipulative treatment is noninvasive and can be used to supplement traditional CTS treatment methods. The authors also review the relevant anatomy involving CTS and the clinical efficacy of osteopathic manipulative medicine in the management of this disorder.